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 network in the rat hippocampal formation, which is not ameliorated by alcohol withdrawal. Following withdrawal from alcohol, there is a further loss of intrinsic hippocampal cholinergic neurons. In this study, we investigated whether treatment with putative neuroprotective agents during the entire withdrawal period would have beneficial effects upon the hippocampal cholinergic innervation. Adult male rats were alcohol-fed for 6 months and subsequently withdrawn from alcohol for 6 months. Some animals were treated with either ganglioside GM1 (35 mg/kg body weight s.c.), vehicle (saline s.c.), or piracetam (800 mg/kg body weight p.o.) for the entire withdrawal period. Choline acetyltransferase (ChAT) immunoreactive (IR) fibers and neurons were analyzed quantitatively in all four animal groups. There were no significant differences in the density of the ChAT-IR hippocampal fiber network when the pure withdrawal and withdrawal + vehicle groups were compared to the withdrawal + GM1 or withdrawal + piracetam groups. In contrast, the number of ChAT-IR interneurons in the hippocampal formation was higher in the withdrawal + 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 cholinergic innervation, but they had a beneficial effect upon the hippocampal intrinsic cholinergic system.
Brandão
F
F
Department of Anatomy, Porto Medical School, Alameda do Prof. Hernâni Monteiro, Portugal.
Ribeiro-da-Silva
A
A
Cadete-Leite
A
A
D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002799:Cholinergic Fibers / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage; D005677:G(M1) Ganglioside / Q000627:therapeutic use*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010889:Piracetam / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D005677:G(M1) Ganglioside; D000431:Ethanol; D010889:Piracetam