Article date: 1987/8/1
PubMed ID: 2443933
Journal name: Pharmacology, biochemistry, and behavior (ISSN: 0091-3057)
The effect of ethanol exposure in vitro on the GABA receptor-operated chloride channel was evaluated by monitoring 36Cl- influx in a membrane vesicle suspension (microsacs) prepared from mouse cerebellum. These experiments directly demonstrate ethanol augmentation of muscimol-stimulated chloride flux. DBA/2J mice were made tolerant to and dependent on ethanol by administration of an ethanol containing liquid diet for 7 days. Exposure to physiologically relevant concentrations of ethanol (10-45 mM) in vitro potentiated muscimol stimulation of 36Cl- uptake in control (pair-fed) membranes, but had no effect on cerebellar microsacs from tolerant/dependent mice. Muscimol stimulation of 36Cl- uptake was not different for pair-fed and ethanol-treated mice. Augmentation of muscimol-induced 36Cl- flux by in vitro ethanol was abolished by a single 4 g/kg injection of ethanol. This “acute tolerance” occurred within 5 min and disappeared within 24 hr after ethanol treatment. The reduced sensitivity of ethanol treated (chronic and acute) mice to ethanol potentiation of muscimol stimulated 36Cl- uptake offers a biochemical correlate to the phenomenon of ethanol tolerance. Moreover, the findings suggest that this biochemical tolerance develops rapidly following a single hypnotic dose of ethanol.
Author List: Allan A M, Harris R A
Publication Types: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Chlorides; Ion Channels; Receptors, GABA-A; Muscimol; Ethanol;
Mesh terms: Animals; Cerebellum/drug effects; Chlorides/pharmacokinetics; Drug Tolerance; Ethanol/pharmacology; Ion Channels/drug effects; Male; Mice; Mice, Inbred DBA; Muscimol/pharmacology; Receptors, GABA-A/drug effects;