The cholinergic system and memory: amelioration of ethanol-induced memory deficiency by physostigmine in rat.

Male Sprague-Dawley rats were treated with a solution of ethanol (20% v/v) as the only source of fluid for 28 weeks while controls received tap water. Profound reductions of acetylcholine content, the activities of choline acetyltransferase and acetylcholinesterase and choline uptake were observed in the cortex, hippocampus, substantia innominata and striatum four weeks after withdrawal from ethanol. These changes in cholinergic markers were accompanied by an impaired performance in a spontaneous alternation task tested at long acquisition-retention intervals. This ethanol induced behavioural deficiency, which most likely represents a memory impairment, could be reversed by application of physostigmine (0.45 g/kg; i.p) whereas neostigmine did not show any behavioural effect. The results suggest that ethanol-induced memory impairment can be ameliorated by pharmacological manipulation of central cholinergic function.