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Eur Neuropsychopharmacol ; 17(4): 277-88, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16989988

RESUMEN

Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central nervous system. High expression in the hippocampus, nucleus accumbens and striatum is consistent with a potential role in cognition and psychosis. The availability of potent, selective and brain-penetrating 5-HT(6) antagonists such as RO4368554 allows further characterization of the role of the 5-HT(6) receptor in these processes. Herein, we tested RO4368554 in several cognition tasks, as well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired adult male rats, RO4368554 was given in novel object discrimination, social recognition, social discrimination, Morris water maze, passive avoidance and autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and 100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3, 10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.) or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion, RO4368554 enhanced learning and memory processes in unimpaired and scopolamine-impaired rats, supporting the notion that the cognitive enhancing effects of 5-HT(6) receptor antagonists involve modulation of cholinergic neurotransmission.


Asunto(s)
Cognición/efectos de los fármacos , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Indoles/farmacología , Indoles/uso terapéutico , Piperazinas/farmacología , Piperazinas/uso terapéutico , Antagonistas de la Serotonina/farmacología , Antagonistas de la Serotonina/uso terapéutico , Estimulación Acústica , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Trastornos Neurológicos de la Marcha/inducido químicamente , Hipocampo/efectos de los fármacos , Hipocampo/lesiones , Hipocampo/fisiopatología , Inhibición Psicológica , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Pruebas Neuropsicológicas , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Escopolamina , Conducta Social
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