Abstract
The effect of ethanol withdrawal on hippocampal acetylcholine (ACh) release was investigated by brain microdialysis in rats rendered ethanol dependent by repeated forced administration of a 20% ethanol solution for 7 days. The behavioral signs of ethanol withdrawal were accompanied by an increase in hippocampal ACh output that was significantly 6 h after the last ethanol administration, reached a maximum (fourfold) at 12 h, and persisted for >72 h. Administration of diazepam (5 mg/kg, i.p.) or γ-hydroxybutyrate (1 g/kg, intragastric) 12 h after the last ethanol administration completely antagonized, within 30 min, the increase in ACh output induced by ethanol withdrawal. Thus, the rapid and marked increase in ACh output might contribute to the changes in cognitive function associated with ethanol withdrawal, and the septohippocampal cholinergic system may play a major role in the response to withdrawal of addictive drugs.
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