Spontaneous Early Withdrawal Behaviors after Chronic 24-hour Free-Choice Access to Ethanol

Aims Abstinence after chronic alcohol consumption leads to withdrawal symptoms, which are exacerbated after repeated cycles of relapse. This study examined withdrawal-like behaviors after chronic ethanol drinking, with or without repeated cycles of deprivation. Methods Male alcohol-preferring (P) rats had access to continuous ethanol (CE), chronic ethanol with repeated deprivation (RD), or remained ethanol naïve (EN). The RD group experienced seven cycles of 2 weeks of deprivation and 2 weeks of re-exposure to ethanol after an initial 6 weeks of ethanol access. Withdrawal was measured after an initial 24 h of ethanol re-exposure in the RD group, which coincided with the same day of ethanol access in the CE group. Withdrawal-like behavior was measured by (a) ethanol intake during the initial 24 h of re-exposure, (b) locomotor activity (LMA) in a novel field 9–13 h after removal of ethanol at the beginning of the fifth re-exposure cycle and (c) acoustic startle responding (ASR) 8–15 h after removal of ethanol at the beginning of the sixth re-exposure cycle. Results The RD rats displayed a 1-h alcohol deprivation effect (ADE) (temporary ethanol increase), relative to CE rats, during the first to fourth and seventh re-exposure cycles. RD and CE rats displayed significant increases in LMA than EN rats. Regarding ASR, RD rats displayed significantly greater ASR relative to EN rats. Conclusion This study confirms that P rats meet the animal model criterion for ethanol-associated dependence, without a reliance on either behavioral (limited fluid access) or pharmacological (seizure threshold manipulation) challenges.

Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents

Background The aim of the study was to determine the effect of caffeine on alcohol consumption with or without deprivation and alcohol-induced conditioned place preference. Methods In the present study, we examined the effects of caffeine (2.5, 5 and 10 mg/kg) on alcohol consumption in Wistar rats with or without periods of deprivation in an unlimited-access, two-bottle, free choice drinking procedure after a stable baseline alcohol consumption was established. Conditioned place preference (CPP) was established by intraperitoneal injections of alcohol (2 g/kg) in a 12-day conditioning schedule in mice. The effect of caffeine (3 mg/kg) on CPP expression was determined by a final post-conditioning test following 12 conditioning sessions with alcohol. The effect of caffeine (3 mg/kg) on the reinstatement of alcohol-induced CPP was determined in a final post-conditioning test following 12 conditioning sessions with alcohol and the extinction of alcohol-induced CPP. Results Alcohol deprivation for 3 days did not result in alcohol deprivation effect (ADE). While caffeine (10 mg/kg) caused a significant (p<0.05) reduction in alcohol consumption compared with the baseline following a period of alcohol deprivation, it did not cause a change in alcohol consumption compared with the baseline in the study without alcohol deprivation phase. Caffeine significantly (p<0.05) reduced the expression of alcohol-induced CPP compared to saline and blocked the reinstatement of alcohol-induced CPP following the injection of a priming dose (0.4 g/kg) of alcohol. Conclusions Given that caffeine is an adenosine receptor antagonist, our findings suggest a role for adenosine receptors in the alcohol reward and alcohol-seeking behaviour.