GM1 and piracetam do not revert the alcohol-induced depletion of cholinergic fibers in the hippocampal formation of the rat

Chronic alcohol consumption causes a depletion of the cholinergic fiber net work in the rat hippocampal formation, which is not ameliorated by alcohol withdrawal. Following withdrawal from alcohol, there is a further loss of i ntrinsic hippocampal cholinergic neurons. In this study, we investigated wh ether treatment with putative neuroprotective agents during the entire with drawal period would have beneficial effects upon the hippocampal cholinergi c innervation. Adult male rats were alcohol-fed for 6 months and subsequent ly withdrawn from alcohol for 6 months. Some animals were treated with eith er ganglioside GM1 (35 mg/kg body weight s.c.), vehicle (saline s.c.), or p iracetam (800 mg/kg body weight p.o.) for the entire withdrawal period. Cho line acetyltransferase (ChAT) immunoreactive (IR) fibers and neurons were a nalyzed quantitatively in all four animal groups. There were no significant differences in the density of the ChAT-IR hippocampal fiber network when t he pure withdrawal and withdrawal + vehicle groups were compared to the wit hdrawal + GM1 or withdrawal + piracetam groups. In contrast, the number of ChAT-IR interneurons in the hippocampal formation was higher in the withdra wal + GM1 or withdrawal + piracetam groups than in the pure withdrawal and withdrawal + Vehicle groups. These results indicate that, in the doses used , neither neuroprotective agent had an effect upon the extrinsic cholinergi c innervation, but they had a beneficial effect upon the hippocampal intrin sic cholinergic system. (C) 1999 Elsevier Science Inc. Ail rights reserved.