GABAA receptor-mediated chloride flux in brain homogenates from rat lines with differing innate alcohol sensitivities

Muscimol stimulation of 36Cl- flux through GABAA receptor-associated ion channels was compared in combined cerebral cortical and cerebellar homogenates from two lines of rats produced by selective outbreeding for high and low alcohol sensitivities. There was no difference in the muscimol effects between ethanol-naive alcohol-sensitive and alcohol-insensitive rats. Acute administration of ethanol (2 g/kg, i.p.) and lorazepam (3 mg/kg, i.p.) significantly reduced the percentage stimulation by muscimol in the alcohol-sensitive animals. The results suggest that genetic selection towards differences in the sensitivity to motor-impairing effects of moderate ethanol doses does not produce alterations in the direct agonist-induced GABAA receptor function. This receptor function was, however, down-regulated in the alcohol-sensitive rats by acute ethanol and benzodiazepine treatments, indicating the involvement of GABAergic activity in the mechanisms of, or in the neural adaptations to, acute intoxication in genetically sensitive animals.