Rewarding and Aversive Doses of Caffeine Alter Activity but Not Conditioned Place Preference Induced by Ethanol in DBA/2J Mice

Increases in the consumption of ethanol and caffeine have been attributed to increased subjective feelings of intoxication and pleasure from the combination. Previous studies have shown that caffeine can be rewarding at low doses and aversive at high doses, although these findings are at times inconsistent between studies using comparable doses. Similarly, studies investigating the rewarding effects of ethanol and caffeine combinations have yielded mixed results. To address this issue, the present experiments were designed to investigate the rewarding effects of caffeine, as well as of caffeine + ethanol combinations. Male DBA/2J mice were exposed to an unbiased conditioned place preference (CPP) procedure with various doses of caffeine (1, 3, 10, 30 mg/kg) and ethanol (1, 2 g/kg), as well as various conditioning trial durations (5, 30, 60 min). Caffeine dose-dependently increased locomotor activity during conditioning, and produced a biphasic effect on place conditioning. Specifically, a low dose of caffeine (3 mg/kg) produced place preference, while a high dose (30 mg/kg) produced place aversion. When combined with alcohol, caffeine dose-dependently increased ethanol's stimulatory effect. However, the addition of caffeine had no effect on ethanol place preference, as there were no differences in the strength of place preference between mice conditioned with ethanol alone, and mice conditioned with any combination of ethanol and caffeine. These studies add evidence for caffeine's biphasic effects while also emphasizing the importance of considering temporal and methodological parameters when using Pavlovian conditioning procedures to study drug combinations.