Acute and chronic ethanol treatments alter GABA receptor-operated chloride channels.
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.
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000493:pharmacokinetics*; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*
D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol