Periadolescent exposure to ethanol and diazepam alters the aversive properties of ethanol in adult mice

Evidence suggests that the developing adolescent brain may be especially vulnerable to long-term neurobehavioral consequences following ethanol exposure and withdrawal. In the present study, we examined the long-term effect of adolescent ethanol withdrawal on a subsequent EtOH-induced conditioned taste aversion (CTA). Periadolescent and adult C3H mice were exposed to 64 h of continuous (single withdrawal) or intermittent (multiple withdrawal) ethanol vapor. Following each ethanol exposure, animals received either 0, 1, 2, or 3 mg/kg diazepam (DZP) in an attempt to counteract the possible effect of ethanol withdrawal. About 6 weeks following ethanol and DZP treatment, animals were tested for an EtOH-induced CTA. As expected, exposure to EtOH during adolescence attenuated the EtOH-induced CTA as compared to controls. Unexpectedly, administration of DZP during withdrawal did not spare but rather mimicked the attenuation of the EtOH-induced CTA seen in animals exposed to ethanol in adolescence. This attenuation was not evident when EtOH and/or DZP was administered in adulthood. Given the similar mode of action of EtOH and DZP on the GABA system, the principal implication of the present findings is that the intoxicating effect of ethanol on the developing brain can result in long-term changes in the aversive properties of EtOH.