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Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation.
Gil-Bea, Francisco J; Domínguez, Jon; García-Alloza, Mónica; Marcos, Beatriz; Lasheras, Berta; Ramírez, María J.
Afiliación
  • Gil-Bea FJ; Department of Pharmacology, School of Medicine, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Neuropharmacology ; 47(2): 225-32, 2004 Aug.
Article en En | MEDLINE | ID: mdl-15223301
We have studied the effects of concomitant blockade of 5-HT(3) and GABA(A) receptors on acetylcholine (ACh) release in the frontal cortex of rats with a selective cholinergic lesion. Lesions were performed by microinjection of the cholinergic toxin 192 IgG-saporin into the nucleus basalis magnocellularis. Single treatment with either the 5-HT(3) receptor antagonist ondansetron, 0.1 microg/kg, or the GABA(A) receptor benzodiazepine site antagonist flumazenil, 10 mg/kg, did not affect ACh release. However, the combined ondansetron + flumazenil administration significantly increased ACh release to a similar extent as a depolarising stimulus with K(+), 100 mM, at both 7 and 30 days post-lesion. Cortical perfusion with the combined ondansetron + flumazenil treatment also increased [(3)H]ACh efflux "in vitro" 30 days after lesion, suggesting that local events within the frontal cortex may participate in the interaction of ondansetron with GABAergic neurons, modulating ACh release in situations of cholinergic hypoactivity. No differences in the expression of 5-HT(3) and GABA(A) receptors in the frontal cortex were found after the cholinergic lesion. These results suggest that a combined ondansetron + flumazenil treatment would contribute to restoring a diminished cholinergic function and may provide a basis for using this treatment in the therapy of cognitive disorders associated with degeneration of the cholinergic system.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Nervioso Parasimpático / Antagonistas de la Serotonina / Corteza Cerebral / Flumazenil / Ondansetrón / Transmisión Sináptica / Moduladores del GABA / Receptores de Serotonina 5-HT3 / Antagonistas de Receptores de GABA-A Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2004 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Nervioso Parasimpático / Antagonistas de la Serotonina / Corteza Cerebral / Flumazenil / Ondansetrón / Transmisión Sináptica / Moduladores del GABA / Receptores de Serotonina 5-HT3 / Antagonistas de Receptores de GABA-A Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2004 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido