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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Neurociencias > Neurofarmacología y conducta > DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista >

Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation
Autor(es) : Gil-Bea, F.J. (Francisco J.)
Dominguez, J. (Jon)
Garcia-Alloza, M. (Mónica)
Marcos, B. (Beatriz)
Lasheras, B. (Berta)
Ramirez, M.J. (María Javier)
Palabras clave : 5-HT3 receptors
GABAa receptors
192 IgG-saporin
Alzheimer’s disease
Nucleus basalis magnocellularis
Fecha incorporación: 2004
Editorial : Elsevier
Versión del editor: http://www.sciencedirect.com/science/article/pii/S0028390804000887
ISSN: 1873-7064
Cita: Gil-Bea FJ, Dominguez J, Garcia-Alloza M, Marcos B, Lasheras B, Ramirez MJ. Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation. Neuropharmacology 2004 Aug;47(2):225-232.
Resumen
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.
Enlace permanente: http://hdl.handle.net/10171/20235
Aparece en las colecciones: DA - Farmacia - Farmacología - Artículos de revista
DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista

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