A growing trend among ethanol drinkers, especially young adults, is to combine caffeinated energy drinks with ethanol during a drinking episode. The primary active ingredient of these mixers is caffeine, which may significantly interact with ethanol. We tested the two hypotheses that caffeine would enhance ethanol-conditioned place preference and also enhance ethanol-stimulated locomotor activity. The interactive pharmacology of ethanol and caffeine was examined in C57BL/6J (B6) mice in a conditioned place preference procedure with 1.75 g/kg ethanol and 3 mg/kg caffeine. Additionally, we used B6 mice to evaluate ethanol/caffeine combinations on locomotor activity using 3 doses of ethanol (1.75, 2.5 and 3.25 g/kg) and 2 two doses of caffeine (3 and 15 mg/kg). Both ethanol and caffeine administered alone increased preference for the drug paired side, though the effect of caffeine was more modest than that of ethanol. The drug combination produced significant place preference itself, but this was not greater than that for ethanol alone. Additionally, the combination of caffeine and ethanol significantly increased locomotion compared to giving either drug alone. The effect was strongest with a stimulatory dose of ethanol (1.75 g/kg) and waned with increasing doses of ethanol. Thus, combinations of caffeine and ethanol had significant conditioned reinforcing and locomotor activating effects in mice.

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