Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation

Neuropharmacology
Francisco J Gil-BeaM J Ramírez

Abstract

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 contrib...Continue Reading

References

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Citations

Nov 7, 2006·Journal of Neuropathology and Experimental Neurology·Monica Garcia-AllozaMaria Javier Ramirez
Mar 16, 2016·Neuroscience and Biobehavioral Reviews·Deepali GuptaMahesh Radhakrishnan
Jan 25, 2005·Neuroscience Letters·Francisco Javier Gil-BeaMaría Javier Ramírez
Oct 13, 2015·Progress in Neurobiology·Yukihiro OhnoMasashi Sasa

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