Alterations in high-affinity choline uptake in brain after acute and chronic ethanol treatment
Hunt, W.A.; Majchrowicz, E.; Dalton, T.K.
Journal of Pharmacology and Experimental Therapeutics 210(2): 259-263
1979
ISSN/ISBN: 0022-3565 PMID: 572419 Document Number: 141859
Previous studies have suggested that alterations in cholinergic function may result from both acute and chronic administration of ethanol. In a further attempt to characterize these effects, high-affinity choline uptake, a parameter related to acetylcholine release, was measured in several areas of the rat brain after acute and chronic ethanol administration. After a single dose of ethanol, high-affinity choline uptake was accelerated in the caudate nucleus and reduced in the hippocampus, with no effect observed in the cerebral cortex, brain stem or nucleus accumbens. These responses could be seen only at high blood ethanol concentrations. They are apparently indirect effects since ethanol added in vitro to the incubating medium was ineffective in influencing choline uptake. The changes induced by ethanol exhibit noncompetitive kinetics. In animals chronically treated with ethanol and rendered ethanol-depenent, no alterations in high-affinity choline uptake were observed in any brain area studied when animals were still intoxicated (prodromal detoxication phase) or during the early phase of the withdrawal syndrome. This suggests the development of tolerance. By 1 day after withdrawal, striatal choline uptake was significantly elevated and lasted over 3 days. By 7 days after withdrawal, control values were once again obtained. Acute and chronic treatment with ethanol apparently leads to alterations in cholinergic function that are region-specific and time-dependent. Based on previous studies, the elevated striatal choline uptake may be a result of a lack of inhibitory dopaminergic input.