Korsakoff's psychosis, like other amnestic and dementing disorders in humans, is accompanied by a degeneration of the cholinergic neurons in the basal forebrain (Arendt et a[., 1983). These neutrons represent the main cholinergic input to the cerebral cortex and hippocampus (Wenk et al.., 1980), and a reduced activity of choline acetyltransferase has been reported in the hippocampus of chronic alcholics (Antuono et al., 1980). However, the pathogenetic link between prolonged consumption of alcohol, degeneration in the cholinergic system and memory dysfunction has not been established so far. Therefore, the aim of the present study was to investigate the influence of chronic ethanol intake on memory, on cholinergic function in the basal forebrain, and on the target regions of basal forebrain cholinergic cells such as the cerebral cortex and hippocampus. Male Sprague-Dawley rats (150-l8Og) were caged in groups of four and given either 20% (v/v) ethanol or tapwater as the only source of fluid. Mean daily consumption was 9.5 g/kg resulting in blood alcohol levels between 40 mg/ 100 ml (daytime) and 120 mg/100 ml (darkness). At certain time points (after 4.8, 18 and 28 weeks of ethanol consumption, and after a 4 week ethanol-week period following 4, 8, 18 and 28 weeks of ethanol intake) animals were killed by decapitation, or for acetylcholine (ACh) determinations by microwave radiation. The brain was rapidly removed and dissected. Enzyme activities were measured using slightly modified standard methods: choline acetyltransferase (ChAT, EC 2.3.1.6.) (Fonnum 1969), acetylcholinesterase (AChE, EC3.1.1.7) (Ellman et al., 1961), pyruvate decarboxylase (PDC, EC 4. I . 1 .1 .) (Dreyfus & Hauser 1965). Synaptosomes were prepared on Percoll gradients (Dunkley et al., 1986) and choline uptake was measured according to Marchbanks (1968). ACh was extracted by formic acid/ acetone (Toru & Aprison, 1066) and determined on a LKB Wallac 125 1 Luminometer (Israel & Lesbats, 1982). Alcohol blood levels were measured with a Lion Alcometer AE-Dl. Protein was determined according to Peterson (1977). Spatial and non-spatial reference and working memory were measured in an eight-arm radial maze (Jarrard, 1983) after a 4 week ethanol-free period following 8, 18 or 28 weeks of ethanol consumption. In the basal forebrain (Fig. 1) ACh levels and PDC activity showed a rather rapid decline, whereas ChAT and AChE activities decreased only slowly with the duration of ethanol intake. Choline uptake declined after an initial increase which might reflect a compensatory mechanism for the reduction in ACh and PDC activity. However, a 4 week ethanol-free period following 4 or 8 weeks of ethanol consumption reversed all changes back to control values. Changes were not fully reversible after 18 weeks of ethanol intake. After a 28 week period of ethanol consumption the decrease in all parameters persisted for the full 4 weeks of measurement. The aquisition of the spatial and non-spatial memory task was unimpaired after 8 weeks of ethanol consumption. However, after 18 weeks, reference and working memory were marginally impaired in the spatial task. After