6533b7d5fe1ef96bd1264f6c

RESEARCH PRODUCT

Enhancement of Hippocampal Acetylcholine Release by Local Ethanol Infusion

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Among the multiple pathological changes in the CNS which are associated with ethanol intoxication (1), an impairment of cognitive functions is one of the most consistent findings. This impairment may be due to a damage of central cholinergic systems. Long-term administration of ethanol causes neurodegenerative changes in the cholinergic basal fore-brain neurons of rats and humans (2), and in the rat, these changes are accompanied by a reduction of the release of acetylcholine (ACh) in the hippocampal and cortical target regions of basal forebrain neurons (3). Moreover, experimental studies have documented that ethanol-induced dysfunctions of memory and learning can be ameliorated by cholinomimetic drugs or by fetal brain transplants which are rich in cholinergic neurons (4,5). As for acute effects of ethanol, several studies from the seventies have demonstrated an inhibition of the central cholinergic transmission after ethanol administration. Thus, concentrations of 50–150 mM ethanol were found to inhibit ACh release from rat cortical slices under basal (6) or stimulated (7) conditions. In vivo, ethanol (1–2 g/kg) depressed cortical and reticular ACh release as measured by the cortical cup technique or in push-pull experiments in rabbits and cats (8,9). In the present study, we wanted to test a possible effect of acute ethanol administration on the activity of the septohippocampal cholinergic fibres which are intimately involved in cognitive functions. For this purpose, we monitored the ACh release in the hippocampus of awake, freely moving rats using the microdialysis technique. In addition, using hippocampal slices, we determined the rate of formation and breakdown of phos-phatidylethanol (PEth), an unusual phospholipid which is formed after ethanol exposure in the brain by the action of phospholipase D (Fig. 1). The results are compatible with a possible role of PEth formation in the delayed effects of local ethanol infusions on ACh release.