DIFFERENTIAL INTERACTION BETWEEN 5-HT3 RECEPTORS AND GABAERGIC NEURONS INHIBITING ACETYLCHOLINE-RELEASE IN RAT ENTORHINAL CORTEX SLICES

The 5-HT3, receptor antagonists, ondansetron, MDL 72222 and granisetro n(0.01-1 mu M), produced a concentration-dependent increase of K+-evok ed [H-3]ACh efflux in slices from rat entorhinal cortex preloaded with [H-3]choline. Bicuculline and flumazenil, antagonists at different si tes of the GABA(A) receptor, also enhanced [H-3]ACh efflux. While the ACh releasing effect of ondansetron was markedly potentiated, in a TTX -sensitive manner, by bicuculline, the effects of MDL 72222 and granis etron were not significantly modified. A qualitatively identical inter action was found by using flumazenil, a GABA(A) antagonist at the benz odiazepine recognition site, in combination with the 5-HT3, receptor a ntagonists. The potentiation by the GABA(A) antagonists of [H-3]ACh ef flux was also observed in a superfusion medium deficient in Cl-. The n onspecific K+-channel blockers TEA and Ba2+ also increased K+-evoked [ H-3]ACh efflux in this preparation but the releasing effect was not mo dified by bicuculline. The results support the functional interaction of ondansetron with GABAergic interneurons in the rat entorhinal corte x, GABA-independent mechanisms may however be involved in the regulati on of cortical cholinergic function by other 5-HT3 receptor antagonist s. (C) 1998 Elsevier Science B.V. All rights reserved.