Sensitivity to ethanol hypnosis and modulation of chloride channels does not cosegregate with pentobarbital...

Several findings suggest that barbiturates and alcohol produce their sedative effects through a common neural and possibly a common genetic mechanism. We tested this hypothesis by examining the correlation between ethanol and pentobarbital sedative effects in individual animals from a genetically heterogeneous population. The duration of pentobarbital-induced hypnosis (sleep-time) was unrelated to the sleep-time produced by ethanol in heterogeneous stock (HS) mice. Therefore, the present study also examined the effect of ethanol, pentobarbital, and flunitrazepam on muscimol-stimulated chloride flux into brain membranes prepared from HS mice selected for differences in pentobarbital- and ethanol-induced sleep-time. Brain membranes from mice selected for differences in ethanol sleep-time were differentially responsive to ethanol- and flunitrazepam-, but not to pentobarbital-induced augmentation of muscimol-stimulated chloride flux. No differences in augmentation of chloride flux by ethanol, pentobarbital, or flunitrazepam were found in membranes prepared from mice differentially sensitive to pentobarbital hypnosis. The ability of muscimol to stimulate chloride uptake was not related to ethanol or pentobarbital sensitivity. These findings suggest that sensitivity to ethanol is not likely to be genetically linked to pentobarbital sensitivity.