As mentioned above, Peris et al. (1997) showed that chronic EtOH treatment, sufficient for decreasing LTP in rats, also increased 3H-GABA release from hippocampal slices in these same animals. These investigators characterized presynaptic auto-receptor modulation of 3H-GABA release in hippocampal slices from control and EtOH-dependent rats. Effects of a GABAB receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] on electrically stimulated 3H-GABA release from superfused hippocampal slices were examined. Baclofen decreased stimulated release in a dose-dependent manner and the antagonist 2-OH-saclofen increased release consistent with the presence of presynaptic GABAB auto-receptors in hippocampus. The GABAA antagonist bicuculline did not significantly modulate basal or stimulated release. Presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased in animals 48 h after withdrawal from EtOH. Using quantitative autoradiographic techniques, the density of 3H-baclofen binding sites in the hippocampus was not affected by chronic EtOH exposure, whereas the density of 3H-bicuculline binding sites was increased by 28% in EtOH-treated rats. These data may explain how chronic EtOH treatment increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after chronic EtOH exposure (Peris et al. 1997).
