Effects of chronic ethanol exposure on GABA receptors and GABA(B) receptor modulation of H-3-GABA release in the hippocampus

Chronic ethanol treatment (CET), sufficient for decreasing long-term potentiation (LTP) in rats, also enhances H-3-GABA release from hippocampal slices in these same animals. The mechanism for an increase in GABA release may involve changes in presynaptic receptors. Therefore, we characterized presynaptic autoreceptor modulation of H-3-GABA release in hippocampal slices from control and CET rats. The effects of a GABA(B), receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] were tested for their ability to modulate electrically stimulated H-3-GABA release from superfused hippocampal slices. Baclofen decreased stimulated release in a dose-dependent manner and 2-OH-saclofen increased release consistent with the existence of presynaptic GABA(B), autoreceptors in hippocampus. The GABA(A) antagonist bicuculline did not significantly modulate basal or stimulated release. When the effects of baclofen and 2-OH-saclofen were measured in animals 48 hr after withdrawal from CET, presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased. In addition, we examined the density of H-3-baclofen and H-3-bicuculline binding in the hippocampal formation using quantitative autoradiographic techniques. We found that the density of H-3-baclofen binding sites was not affected by CET, whereas the density of H-3-bicuculline binding sites was increased by 28% in ethanol-treated rats. These data may explain how CET increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after CET.