Chronic ethanol ingestion produces cholinergic hypofunction in rat brain.

Alterations in cholinergic function due to prolonged ethanol exposure (up to 9 months) were assessed by choline acetyltransferase (ChAT) activity and high-affinity choline uptake (HAChU) in three brain regions of the Long-Evans rat: frontal cortex, parietal cortex, and region of the nucleus basalis of Meynert (NbM). No statistically significant changes were found in ChAT activity in the 3-month group; however, ChAT activity was decreased in both the frontal cortex (-32%) and NbM region (-22%) after 6 months of ethanol exposure. ChAT activity in the parietal cortex was increased 30% after 6 months. Nine months of exposure significantly decreased ChAT activity in all three brain regions. No significant differences were observed in high-affinity choline uptake after 3 months of ethanol exposure. However, after 6 months of ethanol exposure HAChU was decreased to 51% of control values in the frontal cortex. There was a simultaneous increase in HAChU to 43% and 178% of control values in the NbM and parietal cortex, respectively. However, choline uptake was significantly decreased in the frontal cortex and NbM region after 9 months of exposure. The results indicate a neurotoxic effect of prolonged intake of ethanol on the basal forebrain cholinergic projection system, which may cause impairment of cholinergic innervation of target areas of the basal nucleus complex.