Chronic ethanol exposure increases H-3-GABA release in rat hippocampus by presynaptic muscarinic receptor modulation

Background: Chronic ethanol treatment (CET) for 28 weeks significantly incr eases electrically-stimulated H-3-GABA release from hippocampal slices. Thi s increase in GABA release may be one of the mechanisms by which CET decrea ses the magnitude of long-term potentiation (LTP) in the hippocampus. The p resent study examined whether CET increases GABA release via an alteration in heterologous presynaptic cholinergic regulation. Methods: Animals were treated with ethanol or sucrose diet for 28 weeks fol lowed by either no withdrawal or a 48-hr withdrawal period. The electricall y-stimulated H-3-GABA release from preloaded superfused hippocampal slices of naive and CET rats was measured. Results: Carbachol increased H-3-GABA release in a concentration-dependent manner, and atropine modulated H-3-GABA release in a biphasic concentration -dependent manner. Atropine (10 mu M) significantly blocked the effects of carbachol. Oxotremorine, a selective muscarinic receptor agonist, also incr eased H-3-GABA release. Mecamylamine, a selective nicotinic antagonist, did not modulate H-3-GABA release and did not block the effects of carbachol. The effects of these agents were also tested in rats 0 or 48 hrs after with drawal from CET. The biphasic effects of atropine were decreased, whereas t he facilitating effects of carbachol were significantly increased. There we re no changes in the effects of these agents on H-3-acetylcholine release f rom hippocampal slices of CET rats compared to sucrose-treated rats. Conclusion: These results suggest that presynaptic muscarinic receptors fac ilitate GABA release, whereas nicotinic receptors do not play a significant role in modulating GABA release in hippocampus. CET selectively alters pre synaptic muscarinic regulation of GABA release in hippocampus and may help us to further understand the mechanism underlying the disruption of LTP by cET.