Interacción de los receptores NMDA - 5-HT6 en la investigación preclínica de las alteraciones cognitivas relacionadas con la esquizofrenia

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La figura 1 representa la propuesta del efecto que ejerce la administración aguda (A) o subcrónica (B) de un antagonista NMDA (A. NMDA) tanto sobre los diferentes tipos de receptores (R) como en la liberación de los principales neurotransmisores: la serotonina (5-HT), el ácido gamma-aminobutírico (GABA) y el glutamato." ] ] ] "textoCompleto" => "IntroducciónLa esquizofrenia es una enfermedad mental grave y crónica cuya incidencia a nivel mundial es del 1%<a class="elsevierStyleCrossRef" href="#bib0500">1</a>. La investigación de los mecanismos neurofisiológicos asociados a diversos agentes farmacológicos capaces de imitar los síntomas característicos de la esquizofrenia, también se han utilizado como un medio para comprender mejor la base de la patología en modelos animales. Por ejemplo, los antagonistas del receptor NMDA (RNMDA), como la fenciclidina (PCP) y la ketamina, son fármacos que evocan tanto los síntomas positivos como negativos de la esquizofrenia<a class="elsevierStyleCrossRefs" href="#bib0505">2–7</a>.Por otra parte, el receptor 5-HT6 (R5-HT6) perteneciente a la superfamilia de la serotonina (5-HT) se encuentra principalmente en el cuerpo estriado, el tubérculo olfatorio, el núcleo accumbens, así como en el hipocampo<a class="elsevierStyleCrossRefs" href="#bib0535">8–10</a> y en algunas regiones corticales<a class="elsevierStyleCrossRefs" href="#bib0550">11–14</a>. La distribución del R5-HT6 a nivel cortical y del sistema límbico en áreas como el cuerpo estriado fortalece la hipótesis de que este receptor participa en la regulación de diversos trastornos neuropsiquiátricos, incluido el deterioro cognitivo<a class="elsevierStyleCrossRefs" href="#bib0570">15–18</a>.Antagonistas selectivos del R5-HT6 recientemente descubiertos se han propuesto para el tratamiento de los trastornos cognitivos que incluyen el deterioro cognitivo asociado con la esquizofrenia<a class="elsevierStyleCrossRefs" href="#bib0570">15,16</a>.En ese sentido, investigaciones preclínicas actuales con antagonistas del RNMDA han cobrado especial interés, sobre todo, cuando se administran junto con fármacos serotoninérgicos 5-HT6 para tratar de revertir las alteraciones cognitivas. Sin embargo, todavía es poco clara la explicación del efecto procognitivo de los fármacos 5-HT6 (agonistas y antagonistas), en especial cuando se combinan en dosis subóptimas con antagonistas del RNMDA.Por todo lo anterior, el propósito principal de este trabajo fue realizar una revisión de las investigaciones preclínicas más recientes, en donde se utilicen ambos fármacos, antagonistas del RNMDA y fármacos serotoninérgicos 5-HT6, con la finalidad de comprender mejor los posibles mecanismos implicados en la interacción de estos receptores (NMDA - 5-HT6).Investigaciones preclínicas de los antagonistas del RNMDA en diferentes modelos conductualesAlteraciones cognitivas con diversos esquemas farmacológicos de ketamina han sido reportadas en múltiples investigaciones preclínicas (<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>). Por ejemplo, la administración crónica de ketamina (20 y 30mg/kg) por vía intraperitoneal (i. p.) en ratones entre 14-90 días de tratamiento, indujo deterioro en la memoria cuando los animales fueron experimentados en distintas pruebas conductuales como el laberinto en Y (LY), la prueba de inhibición de prepulso (PIP) y el laberinto acuático de Morris (LAM)<a class="elsevierStyleCrossRefs" href="#bib0590">19–21</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Por otro lado, la administración subcrónica de ketamina (30mg/kg i. p.) en roedores durante un periodo de 5 o 10 días, también fue capaz de inducir alteraciones en la memoria en modelos conductuales como el modelo de reconocimiento de un objeto nuevo (MRON)<a class="elsevierStyleCrossRefs" href="#bib0605">22,23</a>, la prueba de cambio de tarea (PCT)<a class="elsevierStyleCrossRef" href="#bib0615">24</a>, la prueba de escarbamiento condicionado (PEC)<a class="elsevierStyleCrossRef" href="#bib0620">25</a>, la prueba de reconocimiento de olores (PRO)<a class="elsevierStyleCrossRef" href="#bib0625">26</a> y LAM<a class="elsevierStyleCrossRef" href="#bib0630">27</a>. Asimismo, la administración aguda de ketamina en dosis más altas (100mg/kg i. p.) indujo deterioro cognitivo en el LAM<a class="elsevierStyleCrossRef" href="#bib0635">28</a>. Es notable el predominio de los tratamientos subcrónicos con los antagonistas del RNMDA y la capacidad de los mismos para inducir alteraciones cognitivas.Así también, cuando se inyectó una dosis aguda de otro antagonista del RNMDA, el MK-801, en dosis que oscilaban entre 0,1-1,0mg/kg por vía i. p. o subcutánea en roedores, también se observó deterioro cognitivo cuando los animales fueron experimentados en el MRON (<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>)<a class="elsevierStyleCrossRefs" href="#bib0640">29–32</a>. Además, la inyección aguda y subcrónica de PCP en roedores, en dosis que fluctuaban entre 1-10mg/kg administradas por las misma vías anteriormente descritas presentaron deterioro cognitivo en el mismo modelo (<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>)<a class="elsevierStyleCrossRefs" href="#bib0660">33–36</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Investigaciones preclínicas de fármacos 5-HT6 en distintos modelos conductualesComo se puede observar en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>, la inyección de dosis aguda o subcrónicas de diversos antagonistas 5-HT6 como el SB-271046, SB-317114, el Ro-046790, etc., en dosis que oscilaban entre 1-30mg/kg, administradas por vía oral o intraperitoneal ejercieron un efecto procognitivo cuando los animales fueron experimentados en diferentes pruebas conductuales de: reconocimiento social (PRS)<a class="elsevierStyleCrossRef" href="#bib0680">37</a>, espontaneidad (PE)<a class="elsevierStyleCrossRef" href="#bib0685">38</a>, automoldeamiento (PAM)<a class="elsevierStyleCrossRef" href="#bib0690">39</a>, LAM<a class="elsevierStyleCrossRefs" href="#bib0695">40–42</a> y MRON<a class="elsevierStyleCrossRefs" href="#bib0705">42–45</a>. Destaca la prevalencia de estudios con esquemas agudos y el uso de diversos antagonistas del R5-HT6, además de que se observan escasos estudios con agonistas de este receptor, como lo reportado por Kendal et al.<a class="elsevierStyleCrossRef" href="#bib0715">44</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Interacción de los receptores NMDA-5-HT6 en modelos experimentales para el estudio de la esquizofreniaTodos los estudios que se analizan en la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> se realizaron en ratas. La administración subcrónica de PCP en diferentes dosis (1-5mg/k) inyectadas por 5 y 7 días indujeron deterioro cognitivo en 2 modelos de condicionamiento, la caja de Eskiner y la tarea de configuración cambiante (TCC). Este deterioro fue revertido con la administración aguda e individualizada de 2 antagonistas 5-HT6 (GSK-742457 y SB271046)<a class="elsevierStyleCrossRefs" href="#bib0725">46,47</a>. Coincidentemente, 2 esquemas farmacológicos, uno agudo y otro subcrónico, de distintos antagonistas NMDA (PCP y ketamina) fueron administrados en ratas, las cuales presentaron alteraciones en la PIP<a class="elsevierStyleCrossRefs" href="#bib0735">48,49</a>, desafortunadamente ningún antagonista del R5-HT6 fue capaz de revertir esta alteración.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Por otra parte, la administración subcrónica de PCP o ketamina (7 y 10 días) en ratas que se experimentaron en el MRON, también indujo alteraciones en la memoria, mientras que dosis individualizadas y agudas de un agonista (EMD 386088) o un antagonista (Lu AE58054) del R5-HT6 lograron revertir esta alteración cognitiva<a class="elsevierStyleCrossRefs" href="#bib0740">49,50</a>. Por el contrario, ratas experimentadas en un modelo cognitivo similar y que fueron tratadas con una dosis aguda del antagonista MK-801, presentaron deterioro en la memoria, que no pudo ser prevenido con la administración del antagonista del R5-HT6 (Ro 04-6790)<a class="elsevierStyleCrossRef" href="#bib0720">45</a>.Finalmente, es sorprendente que la administración conjunta de dosis agudas y subóptimas tanto de un antagonista del RNMDA (memantina) como de un agonista del R5-HT6 (E-6801), logró mejorar la memoria de ratas experimentadas en el MRON<a class="elsevierStyleCrossRef" href="#bib0715">44</a>.Análisis de los trabajos revisadosLas neuronas serotoninérgicas del núcleo del rafe dorsal (RD) se proyectan hacia diversas regiones cerebrales, como el hipocampo y la corteza prefrontal (CPF). En el RD el RNMDA induce corrientes postsinápticas inhibitorias<a class="elsevierStyleCrossRef" href="#bib0750">51</a>, lo que sugiere que el antagonismo de este receptor podría aumentar la actividad neuronal del rafe<a class="elsevierStyleCrossRefs" href="#bib0755">52–54</a>, y condicionaría a un incremento en la liberación de 5-HT<a class="elsevierStyleCrossRef" href="#bib0770">55</a>. Acorde con esta última idea, la PCP fue capaz de inducir un aumento en la producción de 5-HT extracelular en la CPF y en el hipocampo dorsal<a class="elsevierStyleCrossRefs" href="#bib0770">55,56</a>.Otros estudios también han demostrado una estrecha relación entre la función del RNMDA y la actividad serotoninérgica. Por ejemplo, diversos trabajos señalan que 2 antagonistas del RNMDA (MK-801 y PCP) pueden disminuir tanto los niveles de la 5-HT como su metabolito, el ácido 5-hidroxi-indol-acético en la CPF, el hipocampo, y otras regiones cerebrales<a class="elsevierStyleCrossRefs" href="#bib0775">56–60</a>. Mientras que Dall’Olio et al. (2000)<a class="elsevierStyleCrossRef" href="#bib0800">61</a> demostraron que dcycloserina, un modulador positivo del RNMDA, inhibió la función serotoninérgica.Por otra parte, la administración aguda de un antagonista del RNMDA, la PCP, indujo un aumento significativo en los niveles extracelulares de glutamato en la CPF<a class="elsevierStyleCrossRefs" href="#bib0805">62,63</a>, coincidentemente, esta región cerebral se ha involucrado críticamente en la cognición<a class="elsevierStyleCrossRefs" href="#bib0815">64,65</a> e implicado en las alteraciones cognitivas de la esquizofrenia<a class="elsevierStyleCrossRefs" href="#bib0820">65–67</a>.El aumento de glutamato en la CPF inducido por los antagonistas del RNMDA pudiera ser atribuible a este receptor localizado en las interneuronas GABAérgicas, lo que conduciría a una menor actividad de estas neuronas y a una desinhibición en la liberación de glutamato<a class="elsevierStyleCrossRefs" href="#bib0805">62,68–70</a>.La hipótesis anterior se plantea tomando en consideración los estudios que han demostrado tanto in vitro como in vivo el efecto que ejercen los antagonistas NMDA sobre algunos marcadores de la función GABAérgica, como la enzima descarboxilasa del ácido glutámico 67 (GAD67)<a class="elsevierStyleCrossRefs" href="#bib0850">71–75</a>. Curiosamente, las perturbaciones en los sistemas GABAérgicos, incluidas las reducciones en parvalbúmina y GAD67 en la CPF, también se han encontrado en los pacientes esquizofrénicos<a class="elsevierStyleCrossRefs" href="#bib0875">76–80</a>.En contraste, la administración subcrónica de MK-801 y PCP de forma independiente, indujeron una disminución en los niveles extracelulares de glutamato en la CPF<a class="elsevierStyleCrossRefs" href="#bib0805">62,81,82</a>, lo cual podría revelar una aparente tolerancia parcial a dosis repetidas del antagonista del RNMDA<a class="elsevierStyleCrossRef" href="#bib0805">62</a>. En esta misma línea, la administración crónica de 2,5mg/kg durante un mes, también redujo los niveles de N-acetil aspartato, glutamato, glicina, lactato y GABA<a class="elsevierStyleCrossRef" href="#bib0910">83</a>.No obstante, es complicado el análisis de los niveles cerebrales de glutamato en los pacientes esquizofrénicos por existir evidencias contradictorias, ya que por un lado, se ha observado una hipofuncionalidad del RNMDA en interneuronas GABAérgicas, lo que conlleva a una desinhibición para la liberación de glutamato en diferentes regiones cerebrales, incluida la CPF<a class="elsevierStyleCrossRefs" href="#bib0915">84,85</a>. También se ha descrito una mayor expresión del mRNA del transportador de glutamato EAAT2 tanto en tálamo como en la CPF de pacientes esquizofrénicos<a class="elsevierStyleCrossRefs" href="#bib0925">86,87</a>, lo cual alude a la idea de una mayor actividad en este sistema de transporte y por lo tanto, a una disminución en la disponibilidad de glutamato, así como en la neurotransmisión glutamatérgica.Retomando la interacción de los receptores NMDA y 5-HT6, es interesante mencionar un estudio con la administración subcrónica del antagonista MK-801 en ratas, en donde se encontró una disminución significativa en la expresión del mRNA del R5-HT6 en el cuerpo estriado, lo cual se explicó mediante el efecto indirecto que pudiera ejercer el antagonista NMDA sobre las neuronas GABAérgicas, lo que condicionaría a un incremento en la liberación de 5-HT al nivel postsináptico y consecuentemente a una regulación a la baja del R5-HT6<a class="elsevierStyleCrossRef" href="#bib0935">88</a>.Con base en lo anterior, es posible que la administración aguda de algún antagonista del RNMDA ejerza, tanto de manera directa como indirecta, un aumento en la liberación de 5-HT en las regiones postsinápticas como el cuerpo estriado y la CPF, partiendo de que el RNMDA se encuentra localizado tanto en neuronas serotoninérgicas en los núcleos del RD, como en interneuronas GABAérgicas (<a class="elsevierStyleCrossRef" href="#fig0005">fig. 1</a>A). Por otro lado, el incremento en los niveles de serotonina en regiones postsinápticas pudiera sobreestimular la exocitosis de glutamato en regiones de la CPF. El exceso de glutamato liberado podría afectar la cognición mediante la estimulación de otro tipo de receptores a glutamato como los mGlu2/3<a class="elsevierStyleCrossRefs" href="#bib0940">89–91</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>En otro contexto, el deterioro cognitivo asociado al tratamiento subcrónico de antagonistas del RNMDA que se ha descrito en varios estudios, pudiera explicarse a través de una disminución en la liberación de glutamato en áreas postsinápticas, incluida la CPF<a class="elsevierStyleCrossRefs" href="#bib0805">62,83</a>. A su vez, esta disminución en los niveles extracelulares de glutamato pudiera asociarse con la disminución en la expresión del R5-HT6<a class="elsevierStyleCrossRef" href="#bib0935">88</a>. Esta hipótesis se reforzaría tomando en consideración el efecto apoptótico inducido por tratamientos subcrónicos de antagonistas del RNMDA en el hipocampo y la CPF, regiones altamente relacionadas con la regulación de la memoria<a class="elsevierStyleCrossRefs" href="#bib0630">27,92–96</a>.En la mayoría de los estudios anteriormente revisados con fármacos serotoninérgicos 5-HT6 se pudo observar la capacidad de estos para revertir las alteraciones cognitivas inducidas por esquemas subcrónicos de los antagonistas del RNMDA, condición que podría estar relacionada con las propiedades de los fármacos serotoninérgicos 5-HT6 para reestablecer la aparente hipoactividad glutamatérgica asociada al deterioro cognitivo. La idea anterior podría ser fundamentada por el efecto sumatorio procognitivo observado tras la administración conjunta de dosis subóptimas de un antagonista NMDA y un fármaco 5-HT6<a class="elsevierStyleCrossRef" href="#bib0715">44</a>; lo cual hace suponer que ambos compuestos tienen injerencia sobre la liberación de glutamato (<a class="elsevierStyleCrossRef" href="#fig0005">fig. 1</a>B).Finalmente, es interesante considerar dentro de las posibles interacciones de ambos sistemas de los receptores NMDA y 5-HT6 la capacidad que tienen tanto los antagonistas del RNMDA como los agonistas del R5-HT6 para interactuar con las proteínas diana de la rapamicina (por sus siglas en inglés mTOR) en neuronas de la CPF<a class="elsevierStyleCrossRefs" href="#bib0980">97,98</a>, las cuales han sido relacionadas directamente con la formación y maduración de nuevas espinas sinápticas implicadas en la plasticidad neuronal y en la memoria<a class="elsevierStyleCrossRef" href="#bib0990">99</a>. Ante el número insuficiente de estudios sobre esta problemática, se podría proponer en el futuro estudiar el efecto de los tratamientos subcrónicos con los antagonistas NMDA sobre los niveles de mTOR en regiones de la CPF, lo cual ayudaría a comprender mejor los mecanismos implicados en el deterioro cognitivo en animales tratados con esquemas subcrónicos de los antagonistas del RNMDA.ConclusionesEs evidente que el esquema farmacológico basado en la administración subcrónica de los antagonistas del NMDAR representa un modelo integrador que permite vislumbrar diferentes tipos de alteraciones cognitivo-conductuales de larga duración, propias de la esquizofrenia, lo cual podría ser mayormente aplicado en las investigaciones preclínicas de las propiedades procognitivas de nuevos fármacos serotoninérgicos 5-HT6.La interacción de los receptores NMDA y 5-HT6 pudiera confluir en la regulación tanto directa como indirecta para la liberación de glutamato, 5-HT y dopamina. Esta interacción en la regulación glutamatérgica por parte de ambos receptores pudiera explicar la reversión de las alteraciones cognitivas por los fármacos serotoninérgicos 5-HT6 en ratones previamente tratados con antagonistas NMDA. Sin embargo, estos mecanismos todavía resultan complejos y requieren mayor profundidad en el estudio de varios elementos coincidentes como: la localización, la determinación de los cambios en los niveles extracelulares de 5-HT, GABA y glutamato en distintas regiones cerebrales, tras la estimulación o el antagonismo de los receptores NMDA y 5-HT6, lo cual fundamentaría mejor las hipótesis planteadas en este trabajo.Conflicto de interesesLos autores declaran no tener ningún conflicto de intereses." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres525589" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec545796" "titulo" => "Palabras clave" ] 2 => array:3 [ "identificador" => "xres525588" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec545795" "titulo" => "Keywords" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introducción" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Investigaciones preclínicas de los antagonistas del RNMDA en diferentes modelos conductuales" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Investigaciones preclínicas de fármacos 5-HT6 en distintos modelos conductuales" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Interacción de los receptores NMDA-5-HT6 en modelos experimentales para el estudio de la esquizofrenia" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Análisis de los trabajos revisados" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusiones" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicto de intereses" ] 11 => array:1 [ "titulo" => "Bibliografía" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-01-24" "fechaAceptado" => "2015-02-10" "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec545796" "palabras" => array:6 [ 0 => "Receptor NMDA" 1 => "Receptor 5-HT6" 2 => "Deterioro cognitivo" 3 => "Serotonina" 4 => "Glutamato" 5 => "Esquizofrenia" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec545795" "palabras" => array:6 [ 0 => "NMDA receptor" 1 => "5-HT6 receptor" 2 => "Cognitive impairment" 3 => "Serotonin" 4 => "Glutamate" 5 => "Schizophrenia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Diversos antagonistas del receptor N-metil-D-aspartato (RNMDA) como la fenciclidina o la ketamina estudiados en roedores han permitido inducir alteraciones cognitivas similares a las observadas en la esquizofrenia. Casualmente, uno de los receptores a serotonina, el 5-HT6, ha cobrado interés en la búsqueda de nuevos fármacos con propiedades procognitivas.Con la finalidad de comprender mejor la interacción de ambos receptores (NMDA y 5-HT6) en la regulación cognitiva se realizó una revisión exhaustiva en la literatura.Varios estudios con esquemas agudos o subcrónicos de los antagonistas NMDA en roedores fueron evaluados en distintas pruebas, en donde se encontró deterioro cognitivo. Fue común que el esquema agudo de diversos fármacos serotoninérgicos 5-HT6 revirtiera el deterioro cognitivo inducido por la administración previa de los antagonistas del RNMDA. Por el contrario y sorprendentemente, la inyección aguda y combinada tanto de los antagonistas NMDA como de los fármacos serotoninérgicos 5-HT6 lograron fortalecer la memoria.El esquema subcrónico de los antagonistas NMDA representa el modelo más integrador para el estudio de las alteraciones cognitivas asociadas a la esquizofrenia. Aunque el deterioro y el efecto procognitivo mediados por estos receptores pudieran ser explicados mediante la regulación conjunta que ejercen ambos receptores sobre la liberación de distintos neurotransmisores como el glutamato, es una situación compleja que se requiere continuar investigando para fundamentar mejor estas ideas." ] "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Diverse antagonists of the NMDA receptor studied in rodents, such as phencyclidine or ketamine, have enabled researchers to induce cognitive changes similar to those found in schizophrenia. Interestingly, one of the serotonin receptors, 5-HT6, has attracted much attention for the development of new drugs with pro-cognitive properties. With the aim of better understanding the interaction of both NMDA and 5-HT6 in cognitive regulation, an exhaustive review of the literature was carried out.Various studies have found cognitive impairment, evaluated in rodents using different tests, after applying acute or sub-chronic schemes of NMDA antagonists. An acute scheme of applying different serotogenic 5-HT6 receptors has often reversed the cognitive impairment induced by the previous administration of NMDA antagonists. Surprisingly, an acute injection of a combination of suboptimal doses of NMDA and 5-HT6 antagonists resulted in strengthening memory.The sub-chronic scheme of NMDA antagonists represents the most reliable model for the study of cognitive changes associated with schizophrenia. Cognitive impairment, as well as a pro-cognitive effect mediated by NMDA and 5-HT6, may be explained by a joint regulation of these receptors to modulate the release of distinct neurotransmitters, such as glutamate. This represents a complex interaction that requires ongoing research to clarify the mechanisms at play." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1250 "Ancho" => 2333 "Tamanyo" => 163619 ] ] "descripcion" => array:1 [ "es" => "Múltiples sistemas de neurotransmisión involucrados en la interacción de los receptores NMDA - 5-HT6. La figura 1 representa la propuesta del efecto que ejerce la administración aguda (A) o subcrónica (B) de un antagonista NMDA (A. NMDA) tanto sobre los diferentes tipos de receptores (R) como en la liberación de los principales neurotransmisores: la serotonina (5-HT), el ácido gamma-aminobutírico (GABA) y el glutamato." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Tabla 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "En la tabla 1 se observa el efecto de la administración aguda o subcrónica de ketamina administrada por vía intraperitonial (i. p.) en ratones y ratas macho que fueron experimentados en diversos modelos conductuales: laberinto en Y (LY), prueba de inhibición de prepulso (PIP), laberinto acuático de Morris (LAM), modelo de reconocimiento de un objeto nuevo (MRON), prueba de cambio de tarea (PCT), prueba de escarbamiento condicionado (PEC) y prueba de reconocimiento de olores (PRO)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudio \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unidadexperimental \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fármaco \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosis(mg/kg i. p.) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Periodo de administración (en días) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Modelo conductual</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Efecto \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Monte et al.<a class="elsevierStyleCrossRef" href="#bib0590">19</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ratones \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ketamina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">LY \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PIP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Deterioro cognitivo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Huang et al.<a class="elsevierStyleCrossRef" href="#bib0595">20</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">LAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tan et al.<a class="elsevierStyleCrossRef" href="#bib0600">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hou et al.<a class="elsevierStyleCrossRef" href="#bib0605">22</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Enomoto y Floresco<a class="elsevierStyleCrossRef" href="#bib0615">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ratas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Nikiforuk y Popik<a class="elsevierStyleCrossRef" href="#bib0620">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PEC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Jacklin et al.<a class="elsevierStyleCrossRef" href="#bib0610">23</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rushforth et al.<a class="elsevierStyleCrossRef" href="#bib0625">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 y 30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PRO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Wang et al.<a class="elsevierStyleCrossRef" href="#bib0630">27</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">LAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Liu et al.<a class="elsevierStyleCrossRef" href="#bib0635">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab847468.png" ] ] ] ] "descripcion" => array:1 [ "es" => "Investigaciones preclínicas del efecto de ketamina sobre la cognición en diferentes modelos conductuales" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Tabla 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "En la tabla 2 se observa el efecto de la administración aguda o subcrónica de 2 antagonistas NMDA, el MK-801 y la fenciclidina (PCP), los cuales fueron administrados por vía intraperitoneal (i. p.) o subcutánea (s. c.) en roedores que se experimentaron en el modelo de reconocimiento de un objeto nuevo (MRON)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudio \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unidadexperimental \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fármaco \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Esquemafarmacológico \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Modelo conductual \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Efecto \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Park et al.<a class="elsevierStyleCrossRef" href="#bib0640">29</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ratones \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MK-801 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0,2mg/kg i. p. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Deterioro cognitivo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rogóz<a class="elsevierStyleCrossRef" href="#bib0645">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Wieronska et al.<a class="elsevierStyleCrossRef" href="#bib0650">31</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0,1mg/kg s. c. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Callahan et al.<a class="elsevierStyleCrossRef" href="#bib0655">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ratas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1mg/kg i. p. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Popik et al.<a class="elsevierStyleCrossRef" href="#bib0660">33</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ratas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PCP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5mg/kg i. p. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Deterioro cognitivo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Grayson et al.<a class="elsevierStyleCrossRef" href="#bib0665">34</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 o 2mg/kg i. p. x7 días \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Horiguchi et al.<a class="elsevierStyleCrossRef" href="#bib0670">35</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Horio et al.<a class="elsevierStyleCrossRef" href="#bib0675">36</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ratones \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10mg/kg s. c. x10 días \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab847467.png" ] ] ] ] "descripcion" => array:1 [ "es" => "Administración de otros antagonistas NMDA y su impacto sobre la memoria en el MRON" ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Tabla 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "En la tabla 3 se observa el efecto cognitivo de la administración aguda y subcrónica de diversos antagonistas y agonistas 5-HT6 administrados por vía oral (v. o.) e intraperitoneal (i. p.) en ratas macho. Los animales fueron evaluados en pruebas conductuales como: la prueba de reconocimiento social (PRS), la prueba de espontaneidad (PE), prueba de automoldeamiento (PAM), laberinto acuático de Morris (LAM) y el modelo de reconocimiento de un objeto nuevo (MRON)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudio \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fármaco \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Esquemafarmacológico \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Modeloconductual \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Efecto \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Loiseau et al.<a class="elsevierStyleCrossRef" href="#bib0680">37</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-258585 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 o 20mg/kg i. p. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PRS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Procognitivo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-271046 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mohler et al.<a class="elsevierStyleCrossRef" href="#bib0685">38</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PRX- 07034 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 y 3mg/kg i. p. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Perez-García y Meneses<a class="elsevierStyleCrossRef" href="#bib0690">39</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-357134 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 y 30mg/kg v. o. x7 días \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-391885 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Woolley et al.<a class="elsevierStyleCrossRef" href="#bib0695">40</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ro-046790 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 y 30mg/kg i. p x3 días \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">LAM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rogers y Hagan<a class="elsevierStyleCrossRef" href="#bib0700">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-357134 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 y 10mg/kg v. o. x7 días \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-271046 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stean et al.<a class="elsevierStyleCrossRef" href="#bib0705">42</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SB-357134 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10mg/kg i. p. x1 día \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mitchel et al.<a class="elsevierStyleCrossRef" href="#bib0710">43</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BGC20-761 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Kendall et al.<a class="elsevierStyleCrossRef" href="#bib0715">44</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">E-6837 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">King et al.<a class="elsevierStyleCrossRef" href="#bib0720">45</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ro-046790 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab847465.png" ] ] ] ] "descripcion" => array:1 [ "es" => "Investigaciones preclínicas de fármacos 5-HT6 en distintos modelos conductuales" ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Tabla 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "En la tabla 4 se observa el efecto de la administración aguda y subcrónica de algunos antagonistas NMDA como fenilcilcidina (PCP), ketamina y memantadina sobre la memoria en ratas macho, los cuales fueron administrados por diferentes vías: oral (v. o.), subcutánea (s. c.) e intraperitoneal (i. p.). A demás de la administración conjunta de dosis agudas de diversos fármacos serotoninérgicos 5-HT6. El efecto fue evaluado en distintas pruebas conductuales como: la tarea de configuración cambiante (TCC), la prueba de inhibición de prepulso (PIP), modelo de reconocimiento de un objeto nuevo (MRON), etc." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Estudio \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Esquema farmacológico</th><th class="td" title="table-head " align="left" valign="top" scope="col">Modeloconductual \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Efecto \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Antagonistas NMDA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fármacoserotoninérgico 5-HT6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">De Bruin et al.<a class="elsevierStyleCrossRef" href="#bib0725">46</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PCP (1 y 2mg/kg; s. c. -30min) x5 días \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Antagonista GSK-742457 (0,63 mg/kg; s. c. - 30min), una dosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Caja de Eskiner \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ambos antagonistas 5-HT6 revirtieron el deterioro cognitivo inducido por la PCP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rodefer et al.<a class="elsevierStyleCrossRef" href="#bib0730">47</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PCP (5mg/kg; i. p.), cada 12h x7 días, seguido de 10 días sin tratamiento \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Antagonista SB271046 (10mg/kg, s. c.), dosis aguda administrada inmediatamente antes de la prueba \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TCC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Leng et al.<a class="elsevierStyleCrossRef" href="#bib0735">48</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PCP (1,5mg/kg, s. c. -30min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ro04-6790 (30mg/kg; i. p. -15min) y Ro65-7199 (30mg/kg; v. o. -120min), dosis aguda \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PIP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ambos antagonistas y el agonista 5-HT6 no lograron revertir la interrupción de la PIP inducido por la PCP y la ketamina de manera respectivaEl agonista y antagonista 5-HT6 contrarrestaron el deterioro en la memoria inducida por la ketamina y la PCP de manera respectiva \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Nikiforuk et al.<a class="elsevierStyleCrossRef" href="#bib0740">49</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ketamina (20mg/kg; i. p. -45 min) x10 días. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Agonista EMD 386088 (5mg/kg; i. p. -30min de la ketamina), dosis aguda \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PIPyMRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Arnt et al.<a class="elsevierStyleCrossRef" href="#bib0745">50</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PCP (2mg/kg; i. p.) x7 días, seguido de 7 días sin tratamiento \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Antagonista Lu AE58054 (5 y 10mg/kg; v. o.-60min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MRON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">King et al.<a class="elsevierStyleCrossRef" href="#bib0720">45</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MK-801 (0,05mg/kg; i. p. -40min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ro 04-6790 (10mg/kg; i. p. -20min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">La inyección previa del antagonista NMDA evita que se presente el efecto procognitivo inducido por el antagonista 5-HT6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Kendall et al.<a class="elsevierStyleCrossRef" href="#bib0715">44</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Memantina (5mg/kg; i. p. -20min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Agonista E-6801 1mg/kg; i. p. -20min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">La combinación de ambos antagonista NMDA y agonista 5-HT6 mejoró la memoria \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab847466.png" ] ] ] ] "descripcion" => array:1 [ "es" => "Interacción de los receptores NMDA-5-HT6 en modelos experimentales para el estudio de la esquizofrenia" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:99 [ 0 => array:3 [ "identificador" => "bib0500" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "¿Es posible modelar esquizofrenia en un modelo animal?" 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Interacción de los receptores NMDA - 5-HT6 en la investigación preclínica de las alteraciones cognitivas relacionadas con la esquizofrenia

Interaction of nmda AND 5-HT6 receptors in the preclinical investigation of schizophrenia-related cognitive changes

Alfredo Briones Arandaa,

Autor para correspondencia

alfred725@hotmail.com

Autor para correspondencia.

, José Eduardo Suárez Santiagob, Manuela Castellanos Péreza, Víctor Manuel Vega Villaa

a Laboratorio de Farmacología, Facultad de Medicina Humana, Universidad Autónoma de Chiapas (UNACH), Chiapas, México

b Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Distrito Federal, México

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          "es" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">M&#250;ltiples sistemas de neurotransmisi&#243;n involucrados en la interacci&#243;n de los receptores NMDA - 5-HT6&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La figura 1 representa la propuesta del efecto que ejerce la administraci&#243;n aguda &#40;A&#41; o subcr&#243;nica &#40;B&#41; de un antagonista NMDA &#40;A&#46; NMDA&#41; tanto sobre los diferentes tipos de receptores &#40;R&#41; como en la liberaci&#243;n de los principales neurotransmisores&#58; la serotonina &#40;5-HT&#41;&#44; el &#225;cido gamma-aminobut&#237;rico &#40;GABA&#41; y el glutamato&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La esquizofrenia es una enfermedad mental grave y cr&#243;nica cuya incidencia a nivel mundial es del 1&#37;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">1</span></a>&#46; La investigaci&#243;n de los mecanismos neurofisiol&#243;gicos asociados a diversos agentes farmacol&#243;gicos capaces de imitar los s&#237;ntomas caracter&#237;sticos de la esquizofrenia&#44; tambi&#233;n se han utilizado como un medio para comprender mejor la base de la patolog&#237;a en modelos animales&#46; Por ejemplo&#44; los antagonistas del receptor NMDA &#40;RNMDA&#41;&#44; como la fenciclidina &#40;PCP&#41; y la ketamina&#44; son f&#225;rmacos que evocan tanto los s&#237;ntomas positivos como negativos de la esquizofrenia<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">2&#8211;7</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Por otra parte&#44; el receptor 5-HT6 &#40;R5-HT6&#41; perteneciente a la superfamilia de la serotonina &#40;5-HT&#41; se encuentra principalmente en el cuerpo estriado&#44; el tub&#233;rculo olfatorio&#44; el n&#250;cleo accumbens&#44; as&#237; como en el hipocampo<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">8&#8211;10</span></a> y en algunas regiones corticales<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">11&#8211;14</span></a>&#46; La distribuci&#243;n del R5-HT6 a nivel cortical y del sistema l&#237;mbico en &#225;reas como el cuerpo estriado fortalece la hip&#243;tesis de que este receptor participa en la regulaci&#243;n de diversos trastornos neuropsiqui&#225;tricos&#44; incluido el deterioro cognitivo<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">15&#8211;18</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Antagonistas selectivos del R5-HT6 recientemente descubiertos se han propuesto para el tratamiento de los trastornos cognitivos que incluyen el deterioro cognitivo asociado con la esquizofrenia<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">15&#44;16</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En ese sentido&#44; investigaciones precl&#237;nicas actuales con antagonistas del RNMDA han cobrado especial inter&#233;s&#44; sobre todo&#44; cuando se administran junto con f&#225;rmacos serotonin&#233;rgicos 5-HT6 para tratar de revertir las alteraciones cognitivas&#46; Sin embargo&#44; todav&#237;a es poco clara la explicaci&#243;n del efecto procognitivo de los f&#225;rmacos 5-HT6 &#40;agonistas y antagonistas&#41;&#44; en especial cuando se combinan en dosis sub&#243;ptimas con antagonistas del RNMDA&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Por todo lo anterior&#44; el prop&#243;sito principal de este trabajo fue realizar una revisi&#243;n de las investigaciones precl&#237;nicas m&#225;s recientes&#44; en donde se utilicen ambos f&#225;rmacos&#44; antagonistas del RNMDA y f&#225;rmacos serotonin&#233;rgicos 5-HT6&#44; con la finalidad de comprender mejor los posibles mecanismos implicados en la interacci&#243;n de estos receptores &#40;NMDA - 5-HT6&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Investigaciones precl&#237;nicas de los antagonistas del RNMDA en diferentes modelos conductuales</span><p id="par0030" class="elsevierStylePara elsevierViewall">Alteraciones cognitivas con diversos esquemas farmacol&#243;gicos de ketamina han sido reportadas en m&#250;ltiples investigaciones precl&#237;nicas &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Por ejemplo&#44; la administraci&#243;n cr&#243;nica de ketamina &#40;20 y 30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; por v&#237;a intraperitoneal &#40;i&#46; p&#46;&#41; en ratones entre 14-90 d&#237;as de tratamiento&#44; indujo deterioro en la memoria cuando los animales fueron experimentados en distintas pruebas conductuales como el laberinto en Y &#40;LY&#41;&#44; la prueba de inhibici&#243;n de prepulso &#40;PIP&#41; y el laberinto acu&#225;tico de Morris &#40;LAM&#41;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">19&#8211;21</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Por otro lado&#44; la administraci&#243;n subcr&#243;nica de ketamina &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46;&#41; en roedores durante un periodo de 5 o 10 d&#237;as&#44; tambi&#233;n fue capaz de inducir alteraciones en la memoria en modelos conductuales como el modelo de reconocimiento de un objeto nuevo &#40;MRON&#41;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">22&#44;23</span></a>&#44; la prueba de cambio de tarea &#40;PCT&#41;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">24</span></a>&#44; la prueba de escarbamiento condicionado &#40;PEC&#41;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">25</span></a>&#44; la prueba de reconocimiento de olores &#40;PRO&#41;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">26</span></a> y LAM<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">27</span></a>&#46; Asimismo&#44; la administraci&#243;n aguda de ketamina en dosis m&#225;s altas &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46;&#41; indujo deterioro cognitivo en el LAM<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">28</span></a>&#46; Es notable el predominio de los tratamientos subcr&#243;nicos con los antagonistas del RNMDA y la capacidad de los mismos para inducir alteraciones cognitivas&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">As&#237; tambi&#233;n&#44; cuando se inyect&#243; una dosis aguda de otro antagonista del RNMDA&#44; el MK-801&#44; en dosis que oscilaban entre 0&#44;1-1&#44;0<span class="elsevierStyleHsp" style=""></span>mg&#47;kg por v&#237;a i&#46; p&#46; o subcut&#225;nea en roedores&#44; tambi&#233;n se observ&#243; deterioro cognitivo cuando los animales fueron experimentados en el MRON &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">29&#8211;32</span></a>&#46; Adem&#225;s&#44; la inyecci&#243;n aguda y subcr&#243;nica de PCP en roedores&#44; en dosis que fluctuaban entre 1-10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg administradas por las misma v&#237;as anteriormente descritas presentaron deterioro cognitivo en el mismo modelo &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0660"><span class="elsevierStyleSup">33&#8211;36</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Investigaciones precl&#237;nicas de f&#225;rmacos 5-HT6 en distintos modelos conductuales</span><p id="par0045" class="elsevierStylePara elsevierViewall">Como se puede observar en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#44; la inyecci&#243;n de dosis aguda o subcr&#243;nicas de diversos antagonistas 5-HT6 como el SB-271046&#44; SB-317114&#44; el Ro-046790&#44; etc&#46;&#44; en dosis que oscilaban entre 1-30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; administradas por v&#237;a oral o intraperitoneal ejercieron un efecto procognitivo cuando los animales fueron experimentados en diferentes pruebas conductuales de&#58; reconocimiento social &#40;PRS&#41;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">37</span></a>&#44; espontaneidad &#40;PE&#41;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">38</span></a>&#44; automoldeamiento &#40;PAM&#41;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">39</span></a>&#44; LAM<a class="elsevierStyleCrossRefs" href="#bib0695"><span class="elsevierStyleSup">40&#8211;42</span></a> y MRON<a class="elsevierStyleCrossRefs" href="#bib0705"><span class="elsevierStyleSup">42&#8211;45</span></a>&#46; Destaca la prevalencia de estudios con esquemas agudos y el uso de diversos antagonistas del R5-HT6&#44; adem&#225;s de que se observan escasos estudios con agonistas de este receptor&#44; como lo reportado por Kendal et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">44</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Interacci&#243;n de los receptores NMDA-5-HT6 en modelos experimentales para el estudio de la esquizofrenia</span><p id="par0050" class="elsevierStylePara elsevierViewall">Todos los estudios que se analizan en la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> se realizaron en ratas&#46; La administraci&#243;n subcr&#243;nica de PCP en diferentes dosis &#40;1-5<span class="elsevierStyleHsp" style=""></span>mg&#47;k&#41; inyectadas por 5 y 7 d&#237;as indujeron deterioro cognitivo en 2 modelos de condicionamiento&#44; la caja de Eskiner y la tarea de configuraci&#243;n cambiante &#40;TCC&#41;&#46; Este deterioro fue revertido con la administraci&#243;n aguda e individualizada de 2 antagonistas 5-HT6 &#40;GSK-742457 y SB271046&#41;<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">46&#44;47</span></a>&#46; Coincidentemente&#44; 2 esquemas farmacol&#243;gicos&#44; uno agudo y otro subcr&#243;nico&#44; de distintos antagonistas NMDA &#40;PCP y ketamina&#41; fueron administrados en ratas&#44; las cuales presentaron alteraciones en la PIP<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">48&#44;49</span></a>&#44; desafortunadamente ning&#250;n antagonista del R5-HT6 fue capaz de revertir esta alteraci&#243;n&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Por otra parte&#44; la administraci&#243;n subcr&#243;nica de PCP o ketamina &#40;7 y 10 d&#237;as&#41; en ratas que se experimentaron en el MRON&#44; tambi&#233;n indujo alteraciones en la memoria&#44; mientras que dosis individualizadas y agudas de un agonista &#40;EMD 386088&#41; o un antagonista &#40;Lu AE58054&#41; del R5-HT6 lograron revertir esta alteraci&#243;n cognitiva<a class="elsevierStyleCrossRefs" href="#bib0740"><span class="elsevierStyleSup">49&#44;50</span></a>&#46; Por el contrario&#44; ratas experimentadas en un modelo cognitivo similar y que fueron tratadas con una dosis aguda del antagonista MK-801&#44; presentaron deterioro en la memoria&#44; que no pudo ser prevenido con la administraci&#243;n del antagonista del R5-HT6 &#40;Ro 04-6790&#41;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">45</span></a><span class="elsevierStyleItalic">&#46;</span></p><p id="par0060" class="elsevierStylePara elsevierViewall">Finalmente&#44; es sorprendente que la administraci&#243;n conjunta de dosis agudas y sub&#243;ptimas tanto de un antagonista del RNMDA &#40;memantina&#41; como de un agonista del R5-HT6 &#40;E-6801&#41;&#44; logr&#243; mejorar la memoria de ratas experimentadas en el MRON<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">44</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">An&#225;lisis de los trabajos revisados</span><p id="par0065" class="elsevierStylePara elsevierViewall">Las neuronas serotonin&#233;rgicas del n&#250;cleo del rafe dorsal &#40;RD&#41; se proyectan hacia diversas regiones cerebrales&#44; como el hipocampo y la corteza prefrontal &#40;CPF&#41;&#46; En el RD el RNMDA induce corrientes postsin&#225;pticas inhibitorias<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">51</span></a>&#44; lo que sugiere que el antagonismo de este receptor podr&#237;a aumentar la actividad neuronal del rafe<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">52&#8211;54</span></a>&#44; y condicionar&#237;a a un incremento en la liberaci&#243;n de 5-HT<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">55</span></a>&#46; Acorde con esta &#250;ltima idea&#44; la PCP fue capaz de inducir un aumento en la producci&#243;n de 5-HT extracelular en la CPF y en el hipocampo dorsal<a class="elsevierStyleCrossRefs" href="#bib0770"><span class="elsevierStyleSup">55&#44;56</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Otros estudios tambi&#233;n han demostrado una estrecha relaci&#243;n entre la funci&#243;n del RNMDA y la actividad serotonin&#233;rgica&#46; Por ejemplo&#44; diversos trabajos se&#241;alan que 2 antagonistas del RNMDA &#40;MK-801 y PCP&#41; pueden disminuir tanto los niveles de la 5-HT como su metabolito&#44; el &#225;cido 5-hidroxi-indol-ac&#233;tico en la CPF&#44; el hipocampo&#44; y otras regiones cerebrales<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">56&#8211;60</span></a>&#46; Mientras que Dall&#8217;Olio et al&#46; &#40;2000&#41;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">61</span></a> demostraron que dcycloserina&#44; un modulador positivo del RNMDA&#44; inhibi&#243; la funci&#243;n serotonin&#233;rgica&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Por otra parte&#44; la administraci&#243;n aguda de un antagonista del RNMDA&#44; la PCP&#44; indujo un aumento significativo en los niveles extracelulares de glutamato en la CPF<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">62&#44;63</span></a>&#44; coincidentemente&#44; esta regi&#243;n cerebral se ha involucrado cr&#237;ticamente en la cognici&#243;n<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">64&#44;65</span></a> e implicado en las alteraciones cognitivas de la esquizofrenia<a class="elsevierStyleCrossRefs" href="#bib0820"><span class="elsevierStyleSup">65&#8211;67</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">El aumento de glutamato en la CPF inducido por los antagonistas del RNMDA pudiera ser atribuible a este receptor localizado en las interneuronas GABA&#233;rgicas&#44; lo que conducir&#237;a a una menor actividad de estas neuronas y a una desinhibici&#243;n en la liberaci&#243;n de glutamato<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">62&#44;68&#8211;70</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">La hip&#243;tesis anterior se plantea tomando en consideraci&#243;n los estudios que han demostrado tanto <span class="elsevierStyleItalic">in vitro</span> como <span class="elsevierStyleItalic">in vivo</span> el efecto que ejercen los antagonistas NMDA sobre algunos marcadores de la funci&#243;n GABA&#233;rgica&#44; como la enzima descarboxilasa del &#225;cido glut&#225;mico 67 &#40;GAD67&#41;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">71&#8211;75</span></a>&#46; Curiosamente&#44; las perturbaciones en los sistemas GABA&#233;rgicos&#44; incluidas las reducciones en parvalb&#250;mina y GAD67 en la CPF&#44; tambi&#233;n se han encontrado en los pacientes esquizofr&#233;nicos<a class="elsevierStyleCrossRefs" href="#bib0875"><span class="elsevierStyleSup">76&#8211;80</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">En contraste&#44; la administraci&#243;n subcr&#243;nica de MK-801 y PCP de forma independiente&#44; indujeron una disminuci&#243;n en los niveles extracelulares de glutamato en la CPF<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">62&#44;81&#44;82</span></a>&#44; lo cual podr&#237;a revelar una aparente tolerancia parcial a dosis repetidas del antagonista del RNMDA<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">62</span></a>&#46; En esta misma l&#237;nea&#44; la administraci&#243;n cr&#243;nica de 2&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg durante un mes&#44; tambi&#233;n redujo los niveles de N-acetil aspartato&#44; glutamato&#44; glicina&#44; lactato y GABA<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">83</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">No obstante&#44; es complicado el an&#225;lisis de los niveles cerebrales de glutamato en los pacientes esquizofr&#233;nicos por existir evidencias contradictorias&#44; ya que por un lado&#44; se ha observado una hipofuncionalidad del RNMDA en interneuronas GABA&#233;rgicas&#44; lo que conlleva a una desinhibici&#243;n para la liberaci&#243;n de glutamato en diferentes regiones cerebrales&#44; incluida la CPF<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">84&#44;85</span></a>&#46; Tambi&#233;n se ha descrito una mayor expresi&#243;n del mRNA del transportador de glutamato EAAT2 tanto en t&#225;lamo como en la CPF de pacientes esquizofr&#233;nicos<a class="elsevierStyleCrossRefs" href="#bib0925"><span class="elsevierStyleSup">86&#44;87</span></a>&#44; lo cual alude a la idea de una mayor actividad en este sistema de transporte y por lo tanto&#44; a una disminuci&#243;n en la disponibilidad de glutamato&#44; as&#237; como en la neurotransmisi&#243;n glutamat&#233;rgica&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Retomando la interacci&#243;n de los receptores NMDA y 5-HT6&#44; es interesante mencionar un estudio con la administraci&#243;n subcr&#243;nica del antagonista MK-801 en ratas&#44; en donde se encontr&#243; una disminuci&#243;n significativa en la expresi&#243;n del mRNA del R5-HT6 en el cuerpo estriado&#44; lo cual se explic&#243; mediante el efecto indirecto que pudiera ejercer el antagonista NMDA sobre las neuronas GABA&#233;rgicas&#44; lo que condicionar&#237;a a un incremento en la liberaci&#243;n de 5-HT al nivel postsin&#225;ptico y consecuentemente a una regulaci&#243;n a la baja del R5-HT6<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">88</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Con base en lo anterior&#44; es posible que la administraci&#243;n aguda de alg&#250;n antagonista del RNMDA ejerza&#44; tanto de manera directa como indirecta&#44; un aumento en la liberaci&#243;n de 5-HT en las regiones postsin&#225;pticas como el cuerpo estriado y la CPF&#44; partiendo de que el RNMDA se encuentra localizado tanto en neuronas serotonin&#233;rgicas en los n&#250;cleos del RD&#44; como en interneuronas GABA&#233;rgicas &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>A&#41;&#46; Por otro lado&#44; el incremento en los niveles de serotonina en regiones postsin&#225;pticas pudiera sobreestimular la exocitosis de glutamato en regiones de la CPF&#46; El exceso de glutamato liberado podr&#237;a afectar la cognici&#243;n mediante la estimulaci&#243;n de otro tipo de receptores a glutamato como los mGlu2&#47;3<a class="elsevierStyleCrossRefs" href="#bib0940"><span class="elsevierStyleSup">89&#8211;91</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">En otro contexto&#44; el deterioro cognitivo asociado al tratamiento subcr&#243;nico de antagonistas del RNMDA que se ha descrito en varios estudios&#44; pudiera explicarse a trav&#233;s de una disminuci&#243;n en la liberaci&#243;n de glutamato en &#225;reas postsin&#225;pticas&#44; incluida la CPF<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">62&#44;83</span></a>&#46; A su vez&#44; esta disminuci&#243;n en los niveles extracelulares de glutamato pudiera asociarse con la disminuci&#243;n en la expresi&#243;n del R5-HT6<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">88</span></a>&#46; Esta hip&#243;tesis se reforzar&#237;a tomando en consideraci&#243;n el efecto apopt&#243;tico inducido por tratamientos subcr&#243;nicos de antagonistas del RNMDA en el hipocampo y la CPF&#44; regiones altamente relacionadas con la regulaci&#243;n de la memoria<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">27&#44;92&#8211;96</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">En la mayor&#237;a de los estudios anteriormente revisados con f&#225;rmacos serotonin&#233;rgicos 5-HT6 se pudo observar la capacidad de estos para revertir las alteraciones cognitivas inducidas por esquemas subcr&#243;nicos de los antagonistas del RNMDA&#44; condici&#243;n que podr&#237;a estar relacionada con las propiedades de los f&#225;rmacos serotonin&#233;rgicos 5-HT6 para reestablecer la aparente hipoactividad glutamat&#233;rgica asociada al deterioro cognitivo&#46; La idea anterior podr&#237;a ser fundamentada por el efecto sumatorio procognitivo observado tras la administraci&#243;n conjunta de dosis sub&#243;ptimas de un antagonista NMDA y un f&#225;rmaco 5-HT6<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">44</span></a>&#59; lo cual hace suponer que ambos compuestos tienen injerencia sobre la liberaci&#243;n de glutamato &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Finalmente&#44; es interesante considerar dentro de las posibles interacciones de ambos sistemas de los receptores NMDA y 5-HT6 la capacidad que tienen tanto los antagonistas del RNMDA como los agonistas del R5-HT6 para interactuar con las prote&#237;nas diana de la rapamicina &#40;por sus siglas en ingl&#233;s mTOR&#41; en neuronas de la CPF<a class="elsevierStyleCrossRefs" href="#bib0980"><span class="elsevierStyleSup">97&#44;98</span></a>&#44; las cuales han sido relacionadas directamente con la formaci&#243;n y maduraci&#243;n de nuevas espinas sin&#225;pticas implicadas en la plasticidad neuronal y en la memoria<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">99</span></a>&#46; Ante el n&#250;mero insuficiente de estudios sobre esta problem&#225;tica&#44; se podr&#237;a proponer en el futuro estudiar el efecto de los tratamientos subcr&#243;nicos con los antagonistas NMDA sobre los niveles de mTOR en regiones de la CPF&#44; lo cual ayudar&#237;a a comprender mejor los mecanismos implicados en el deterioro cognitivo en animales tratados con esquemas subcr&#243;nicos de los antagonistas del RNMDA&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="par0125" class="elsevierStylePara elsevierViewall">Es evidente que el esquema farmacol&#243;gico basado en la administraci&#243;n subcr&#243;nica de los antagonistas del NMDAR representa un modelo integrador que permite vislumbrar diferentes tipos de alteraciones cognitivo-conductuales de larga duraci&#243;n&#44; propias de la esquizofrenia&#44; lo cual podr&#237;a ser mayormente aplicado en las investigaciones precl&#237;nicas de las propiedades procognitivas de nuevos f&#225;rmacos serotonin&#233;rgicos 5-HT6&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">La interacci&#243;n de los receptores NMDA y 5-HT6 pudiera confluir en la regulaci&#243;n tanto directa como indirecta para la liberaci&#243;n de glutamato&#44; 5-HT y dopamina&#46; Esta interacci&#243;n en la regulaci&#243;n glutamat&#233;rgica por parte de ambos receptores pudiera explicar la reversi&#243;n de las alteraciones cognitivas por los f&#225;rmacos serotonin&#233;rgicos 5-HT6 en ratones previamente tratados con antagonistas NMDA&#46; Sin embargo&#44; estos mecanismos todav&#237;a resultan complejos y requieren mayor profundidad en el estudio de varios elementos coincidentes como&#58; la localizaci&#243;n&#44; la determinaci&#243;n de los cambios en los niveles extracelulares de 5-HT&#44; GABA y glutamato en distintas regiones cerebrales&#44; tras la estimulaci&#243;n o el antagonismo de los receptores NMDA y 5-HT6&#44; lo cual fundamentar&#237;a mejor las hip&#243;tesis planteadas en este trabajo&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicto de intereses</span><p id="par0135" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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          "titulo" => "Investigaciones precl&#237;nicas de los antagonistas del RNMDA en diferentes modelos conductuales"
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          "titulo" => "Investigaciones precl&#237;nicas de f&#225;rmacos 5-HT6 en distintos modelos conductuales"
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          "identificador" => "sec0020"
          "titulo" => "Interacci&#243;n de los receptores NMDA-5-HT6 en modelos experimentales para el estudio de la esquizofrenia"
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          "identificador" => "sec0025"
          "titulo" => "An&#225;lisis de los trabajos revisados"
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          "identificador" => "sec0030"
          "titulo" => "Conclusiones"
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        10 => array:2 [
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          "titulo" => "Conflicto de intereses"
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        11 => array:1 [
          "titulo" => "Bibliograf&#237;a"
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    "fechaRecibido" => "2015-01-24"
    "fechaAceptado" => "2015-02-10"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Receptor NMDA"
            1 => "Receptor 5-HT6"
            2 => "Deterioro cognitivo"
            3 => "Serotonina"
            4 => "Glutamato"
            5 => "Esquizofrenia"
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          "clase" => "keyword"
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            0 => "NMDA receptor"
            1 => "5-HT6 receptor"
            2 => "Cognitive impairment"
            3 => "Serotonin"
            4 => "Glutamate"
            5 => "Schizophrenia"
          ]
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diversos antagonistas del receptor N-metil-D-aspartato &#40;RNMDA&#41; como la fenciclidina o la ketamina estudiados en roedores han permitido inducir alteraciones cognitivas similares a las observadas en la esquizofrenia&#46; Casualmente&#44; uno de los receptores a serotonina&#44; el 5-HT6&#44; ha cobrado inter&#233;s en la b&#250;squeda de nuevos f&#225;rmacos con propiedades procognitivas&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Con la finalidad de comprender mejor la interacci&#243;n de ambos receptores &#40;NMDA y 5-HT6&#41; en la regulaci&#243;n cognitiva se realiz&#243; una revisi&#243;n exhaustiva en la literatura&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Varios estudios con esquemas agudos o subcr&#243;nicos de los antagonistas NMDA en roedores fueron evaluados en distintas pruebas&#44; en donde se encontr&#243; deterioro cognitivo&#46; Fue com&#250;n que el esquema agudo de diversos f&#225;rmacos serotonin&#233;rgicos 5-HT6 revirtiera el deterioro cognitivo inducido por la administraci&#243;n previa de los antagonistas del RNMDA&#46; Por el contrario y sorprendentemente&#44; la inyecci&#243;n aguda y combinada tanto de los antagonistas NMDA como de los f&#225;rmacos serotonin&#233;rgicos 5-HT6 lograron fortalecer la memoria&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El esquema subcr&#243;nico de los antagonistas NMDA representa el modelo m&#225;s integrador para el estudio de las alteraciones cognitivas asociadas a la esquizofrenia&#46; Aunque el deterioro y el efecto procognitivo mediados por estos receptores pudieran ser explicados mediante la regulaci&#243;n conjunta que ejercen ambos receptores sobre la liberaci&#243;n de distintos neurotransmisores como el glutamato&#44; es una situaci&#243;n compleja que se requiere continuar investigando para fundamentar mejor estas ideas&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Diverse antagonists of the NMDA receptor studied in rodents&#44; such as phencyclidine or ketamine&#44; have enabled researchers to induce cognitive changes similar to those found in schizophrenia&#46; Interestingly&#44; one of the serotonin receptors&#44; 5-HT6&#44; has attracted much attention for the development of new drugs with pro-cognitive properties&#46; With the aim of better understanding the interaction of both NMDA and 5-HT6 in cognitive regulation&#44; an exhaustive review of the literature was carried out&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Various studies have found cognitive impairment&#44; evaluated in rodents using different tests&#44; after applying acute or sub-chronic schemes of NMDA antagonists&#46; An acute scheme of applying different serotogenic 5-HT6 receptors has often reversed the cognitive impairment induced by the previous administration of NMDA antagonists&#46; Surprisingly&#44; an acute injection of a combination of suboptimal doses of NMDA and 5-HT6 antagonists resulted in strengthening memory&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The sub-chronic scheme of NMDA antagonists represents the most reliable model for the study of cognitive changes associated with schizophrenia&#46; Cognitive impairment&#44; as well as a pro-cognitive effect mediated by NMDA and 5-HT6&#44; may be explained by a joint regulation of these receptors to modulate the release of distinct neurotransmitters&#44; such as glutamate&#46; This represents a complex interaction that requires ongoing research to clarify the mechanisms at play&#46;</p></span>"
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        "etiqueta" => "Figura 1"
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        "descripcion" => array:1 [
          "es" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">M&#250;ltiples sistemas de neurotransmisi&#243;n involucrados en la interacci&#243;n de los receptores NMDA - 5-HT6&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La figura 1 representa la propuesta del efecto que ejerce la administraci&#243;n aguda &#40;A&#41; o subcr&#243;nica &#40;B&#41; de un antagonista NMDA &#40;A&#46; NMDA&#41; tanto sobre los diferentes tipos de receptores &#40;R&#41; como en la liberaci&#243;n de los principales neurotransmisores&#58; la serotonina &#40;5-HT&#41;&#44; el &#225;cido gamma-aminobut&#237;rico &#40;GABA&#41; y el glutamato&#46;</p>"
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        "identificador" => "tbl0005"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">En la tabla 1 se observa el efecto de la administraci&#243;n aguda o subcr&#243;nica de ketamina administrada por v&#237;a intraperitonial &#40;i&#46; p&#46;&#41; en ratones y ratas macho que fueron experimentados en diversos modelos conductuales&#58; laberinto en Y &#40;LY&#41;&#44; prueba de inhibici&#243;n de prepulso &#40;PIP&#41;&#44; laberinto acu&#225;tico de Morris &#40;LAM&#41;&#44; modelo de reconocimiento de un objeto nuevo &#40;MRON&#41;&#44; prueba de cambio de tarea &#40;PCT&#41;&#44; prueba de escarbamiento condicionado &#40;PEC&#41; y prueba de reconocimiento de olores &#40;PRO&#41;&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unidadexperimental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosis&#40;mg&#47;kg i&#46; p&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Periodo de administraci&#243;n &#40;en d&#237;as&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Modelo conductual</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Efecto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Monte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ratones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ketamina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">LY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PIP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Deterioro cognitivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Huang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">LAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Tan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hou et al&#46;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Enomoto y Floresco<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ratas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Nikiforuk y Popik<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PEC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Jacklin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rushforth et al&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 y 30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PRO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Wang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">LAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab847468.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Investigaciones precl&#237;nicas del efecto de ketamina sobre la cognici&#243;n en diferentes modelos conductuales</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabla 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">En la tabla 2 se observa el efecto de la administraci&#243;n aguda o subcr&#243;nica de 2 antagonistas NMDA&#44; el MK-801 y la fenciclidina &#40;PCP&#41;&#44; los cuales fueron administrados por v&#237;a intraperitoneal &#40;i&#46; p&#46;&#41; o subcut&#225;nea &#40;s&#46; c&#46;&#41; en roedores que se experimentaron en el modelo de reconocimiento de un objeto nuevo &#40;MRON&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unidadexperimental&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Esquemafarmacol&#243;gico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Modelo conductual&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Efecto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Park et al&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ratones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MK-801&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Deterioro cognitivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rog&#243;z<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Wieronska et al&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg s&#46; c&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Callahan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ratas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Popik et al&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ratas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Deterioro cognitivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Grayson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 o 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>7 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Horiguchi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Horio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ratones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg s&#46; c&#46; x<span class="elsevierStyleHsp" style=""></span>10 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab847467.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Administraci&#243;n de otros antagonistas NMDA y su impacto sobre la memoria en el MRON</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabla 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">En la tabla 3 se observa el efecto cognitivo de la administraci&#243;n aguda y subcr&#243;nica de diversos antagonistas y agonistas 5-HT6 administrados por v&#237;a oral &#40;v&#46; o&#46;&#41; e intraperitoneal &#40;i&#46; p&#46;&#41; en ratas macho&#46; Los animales fueron evaluados en pruebas conductuales como&#58; la prueba de reconocimiento social &#40;PRS&#41;&#44; la prueba de espontaneidad &#40;PE&#41;&#44; prueba de automoldeamiento &#40;PAM&#41;&#44; laberinto acu&#225;tico de Morris &#40;LAM&#41; y el modelo de reconocimiento de un objeto nuevo &#40;MRON&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Esquemafarmacol&#243;gico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Modeloconductual&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Efecto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Loiseau et al&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-258585&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 o 20<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PRS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Procognitivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-271046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mohler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PRX- 07034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 y 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Perez-Garc&#237;a y Meneses<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-357134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 y 30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg v&#46; o&#46; x<span class="elsevierStyleHsp" style=""></span>7 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-391885&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Woolley et al&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ro-046790&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 y 30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p x<span class="elsevierStyleHsp" style=""></span>3 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">LAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rogers y Hagan<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-357134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 y 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg v&#46; o&#46; x<span class="elsevierStyleHsp" style=""></span>7 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-271046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Stean et al&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SB-357134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg i&#46; p&#46; x<span class="elsevierStyleHsp" style=""></span>1 d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mitchel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BGC20-761&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Kendall et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">E-6837&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">King et al&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ro-046790&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Investigaciones precl&#237;nicas de f&#225;rmacos 5-HT6 en distintos modelos conductuales</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Tabla 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">En la tabla 4 se observa el efecto de la administraci&#243;n aguda y subcr&#243;nica de algunos antagonistas NMDA como fenilcilcidina &#40;PCP&#41;&#44; ketamina y memantadina sobre la memoria en ratas macho&#44; los cuales fueron administrados por diferentes v&#237;as&#58; oral &#40;v&#46; o&#46;&#41;&#44; subcut&#225;nea &#40;s&#46; c&#46;&#41; e intraperitoneal &#40;i&#46; p&#46;&#41;&#46; A dem&#225;s de la administraci&#243;n conjunta de dosis agudas de diversos f&#225;rmacos serotonin&#233;rgicos 5-HT6&#46; El efecto fue evaluado en distintas pruebas conductuales como&#58; la tarea de configuraci&#243;n cambiante &#40;TCC&#41;&#44; la prueba de inhibici&#243;n de prepulso &#40;PIP&#41;&#44; modelo de reconocimiento de un objeto nuevo &#40;MRON&#41;&#44; etc&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Estudio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Esquema farmacol&#243;gico</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Modeloconductual&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Efecto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Antagonistas NMDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F&#225;rmacoserotonin&#233;rgico 5-HT6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">De Bruin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCP &#40;1 y 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; s&#46; c&#46; -30<span class="elsevierStyleHsp" style=""></span>min&#41; x<span class="elsevierStyleHsp" style=""></span>5 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Antagonista GSK-742457 &#40;0&#44;63 mg&#47;kg&#59; s&#46; c&#46; - 30<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; una dosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Caja de Eskiner&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ambos antagonistas 5-HT6 revirtieron el deterioro cognitivo inducido por la PCP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rodefer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCP &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46;&#41;&#44; cada 12<span class="elsevierStyleHsp" style=""></span>h x<span class="elsevierStyleHsp" style=""></span>7 d&#237;as&#44; seguido de 10 d&#237;as sin tratamiento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Antagonista SB271046 &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; s&#46; c&#46;&#41;&#44; dosis aguda administrada inmediatamente antes de la prueba&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">TCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Leng et al&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">48</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCP &#40;1&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; s&#46; c&#46; -30<span class="elsevierStyleHsp" style=""></span>min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ro04-6790 &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -15<span class="elsevierStyleHsp" style=""></span>min&#41; y Ro65-7199 &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; v&#46; o&#46; -120<span class="elsevierStyleHsp" style=""></span>min&#41;&#44; dosis aguda&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PIP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ambos antagonistas y el agonista 5-HT6 no lograron revertir la interrupci&#243;n de la PIP inducido por la PCP y la ketamina de manera respectivaEl agonista y antagonista 5-HT6 contrarrestaron el deterioro en la memoria inducida por la ketamina y la PCP de manera respectiva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Nikiforuk et al&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">49</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ketamina &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -45 min&#41; x<span class="elsevierStyleHsp" style=""></span>10 d&#237;as&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Agonista EMD 386088 &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -30<span class="elsevierStyleHsp" style=""></span>min de la ketamina&#41;&#44; dosis aguda&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PIPyMRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Arnt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCP &#40;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46;&#41; x<span class="elsevierStyleHsp" style=""></span>7 d&#237;as&#44; seguido de 7 d&#237;as sin tratamiento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Antagonista Lu AE58054 &#40;5 y 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; v&#46; o&#46;-60<span class="elsevierStyleHsp" style=""></span>min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MRON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">King et al&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MK-801 &#40;0&#44;05<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -40<span class="elsevierStyleHsp" style=""></span>min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ro 04-6790 &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -20<span class="elsevierStyleHsp" style=""></span>min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">La inyecci&#243;n previa del antagonista NMDA evita que se presente el efecto procognitivo inducido por el antagonista 5-HT6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Kendall et al&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Memantina &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -20<span class="elsevierStyleHsp" style=""></span>min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Agonista E-6801 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#59; i&#46; p&#46; -20<span class="elsevierStyleHsp" style=""></span>min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">La combinaci&#243;n de ambos antagonista NMDA y agonista 5-HT6 mejor&#243; la memoria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Interacci&#243;n de los receptores NMDA-5-HT6 en modelos experimentales para el estudio de la esquizofrenia</p>"
        ]
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    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:99 [
            0 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#191;Es posible modelar esquizofrenia en un modelo animal&#63;"
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                        0 => array:2 [
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Residente&#46;"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "120"
                        "paginaFinal" => "126"
                      ]
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                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "2"
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                        "volumen" => "16"
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              "etiqueta" => "3"
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                      "titulo" => "The selective mGlu5 receptor antagonist MTEP&#44; similar to NMDA receptor antagonists&#44; induces social isolation in rats"
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                      "doi" => "10.1038/sj.npp.1301133"
                      "Revista" => array:6 [
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                        "fecha" => "2007"
                        "volumen" => "32"
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            3 => array:3 [
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              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of ketamine in normal and schizophrenic volunteers"
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                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/S0893-133X(01)00243-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuropsychopharmacology&#46;"
                        "fecha" => "2001"
                        "volumen" => "25"
                        "paginaInicial" => "455"
                        "paginaFinal" => "467"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Animal models of cognitive dysfunction and negative symptoms of schizophrenia&#58; Focus on NMDA receptor antagonism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                      ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacol Ther&#46;"
                        "fecha" => "2010"
                        "volumen" => "128"
                        "paginaInicial" => "419"
                        "paginaFinal" => "432"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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Información del artículo

ISSN: 11345934
Idioma original: Español

DOI:10.1016/j.psiq.2015.03.001

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