Cross-tolerance between ethanol and chlordiazepoxide

Abstract

Drug-induced hypothermia was used to investigate drug tolerance and cross-tolerance. C57BL/6J mice, which were injected with a single dose of chlordiazepoxide (CDP; 30 mg/kg) one day before and reinjected with an equivalent dose of CDP the next day, did not develop tolerance to the drug. However, ethanol-pretreated (3.5 g/kg, 24 hr earlier) mice, when injected with CDP (30 mg/kg), showed cross-tolerance to CDP. The cross-tolerance was short-lived (<48 hr). On the other hand, CDP-pretreated mice (30 mg/kg, 24 hr earlier) did not show cross-tolerance to ethanol. The lack of a reciprocating effect of CDP-pretreatment was not likely to be due to the difference in initial dosage between ethanol and CDP. It may be due to different rates of tolerance development or different mechanisms of actions between CDP and ethanol. Mice chronically treated with ethanol also showed a similar degree of cross-tolerance to CDP compared to those exposed to an acute dose of ethanol.