Tolerance to ethanol and cross-tolerance to pentobarbital and barbital

A chronic regimen of ethanol by intubation, which produced clear tolerance to ethanol-induced hypothermia, ataxia and narcosis, produced only a marginal degree of cross-tolerance to these effects of pentobarbital. The lack of appreciable cross-tolerance to pentobarbital-induced hypothermia and ataxia was also observed over a wide range of test doses. However, cross-tolerance to barbital was observed after chronic treatment with ethanol. Increased rate of drug biotransformation did not contribute significantly to the observed tolerance and cross-tolerance. The difference in the extent of cross-tolerance between ethanol and the two barbiturates is consistent with the hypothesis that there is a degree of specificity in the sites of action of ethanol and other sedative-hypnotic drugs.