Oral Binge-Like Ethanol Pre-Exposure During Juvenile/Adolescent Period Attenuates Ethanol-Induced Conditioned Place Aversion in Rats.

AIMS: To determine if oral ethanol self-administration produces a conditioned place preference (CPP) and to determine if ethanol pre-exposure conditions during the juvenile/adolescent period alter the conditioned effects of ethanol and subsequent ethanol self-administration. SHORT SUMMARY: Modified conditioned place preference paradigm allowed rats to orally self-administer ethanol followed by short duration exposure to conditioning chambers. Ethanol produced a conditioned place aversion even though rats self-administered ethanol following the final conditioning test. Juvenile/adolescent pre-exposure to ethanol decreased the place aversion but did not produce place preference. METHODS: Juvenile/adolescent rats consumed sweetened 5% ethanol in the home-cage either during continuous access or intermittent access with water restriction that promoted binge-like consumption. A control group had water access during the 4-week period. Adult rats were conditioned using a modified CPP paradigm wherein rats were water-restricted overnight before being placed in operant chambers to respond for 5% ethanol for 7 min. Following the operant session, rats were placed in the conditioning chamber for 8 min. After the conditioning post-test, rats self-administered ethanol during daily operant sessions. RESULTS: Ethanol produced a conditioned place aversion in water access rats and the continuous access rats. Binge-like ethanol consumption induced by intermittent access with water restriction abolished the place aversion, but did not allow place preference to develop. After conditioning, continuous access rats self-administered ethanol above ~0.6 g/kg which was similar to rats with binge-like experience via intermittent access. CONCLUSIONS: Results suggest that oral ethanol self-administration elicits aversive properties in this model even though ethanol continues to maintain self-administration. Pre-exposure to ethanol during the juvenile/adolescent period may produce tolerance to ethanol's aversive properties only when consumed in a binge-like manner with water restriction. More exploration is needed to understand how behavioral history can influence sensitivity to ethanol's rewarding and aversive properties and subsequent ethanol consumption or self-administration.

Baclofen blocks yohimbine-induced increases in ethanol-reinforced responding in rats.

Chronic or repeated stress increases alcohol consumption. The GABA-B agonist baclofen decreases alcohol consumption and may be most effective for individuals with comorbid anxiety/stress disorders. The present study sought to determine if baclofen blocks stress-induced increases in ethanol self-administration as modeled by repeated yohimbine injections in rats. Rats were trained to respond for 15% w/v ethanol in operant chambers using a method that applies neither water deprivation nor saccharin/sucrose fading. Following training, the rats received 6 injections of 1.25mg/kg yohimbine were given immediately prior to the operant sessions during a 2-week time period. Subsequently, some rats were pair-matched to receive either 1.25mg/kg yohimbine or saline in the presence of 0.3, 1, and 3mg/kg baclofen prior to sessions. Acquisition of ethanol self-administration was poor. Pretreatment with yohimbine consistently increased responding across repeated injections. Yohimbine's effect on ethanol intake unexpectedly diverged from the effect on responding as the rats failed to consume all reinforcers earned. Smaller doses of baclofen paired with saline injections had no effect on ethanol responding; only 3mg/kg baclofen reduced ethanol self-administration. The smallest baclofen dose of 0.3mg/kg failed to block the yohimbine-induced increase in self-administration. The large baclofen dose of 3mg/kg continued to suppress ethanol self-administration when given with yohimbine. Baclofen 1mg/kg blocked the effect of yohimbine even though it had no effect when given in the absence of yohimbine. Exposure to high ethanol concentrations may induce self-administration only in certain conditions. The dissociation between responding and intake suggests that repeated yohimbine injections may initiate other behavioral or physiological mechanisms that confound its effects as a pharmacological stressor. Furthermore, an optimal baclofen dose range may specifically protect against stress-induced alcohol self-administration, highlighting a specific contribution of GABA-B receptors and a potential therapeutic efficacy of GABA-B agonists at a non-sedating dose.