Caffeine modulates voluntary alcohol intake in mice depending on theaccess conditions: Involvement of adenosine receptors and the role of individual differences

Abstract

Caffeine is the most consumed psychoactive stimulant and the main active ingredient of energy drinks.Epidemiology studies have shown a positive correlation between the consumption of energy drinks and that ofethanol. The popular belief is that caffeine antagonizes the intoxicating effects of alcohol. Both drugs act on theadenosine system but have opposite effects. Caffeine is a methylxanthine that acts as a nonselective adenosinereceptor antagonist, binding to A1and A2Areceptor subtypes. In contrast, ethanol increases extracellular ade-nosinergic tone. The purpose of this study was to examine the impact of a broad range of doses of caffeine and ofselective adenosine A1and A2Areceptor antagonists on voluntary ethanol intake under different ethanol accessconditions. C57BL/6 J male mice had access to ethanol (10% w/v) under different conditions: restricted (2 h inthe dark), unrestricted (24 h access), or after 4 days of alcohol removal following several periods of unrestrictedaccess. Mice reduced ethanol intake in the restricted access condition after receiving caffeine (20.0 mg/kg), ortheophylline (20.0 mg/kg), another methylxanthine. Selective A1and A2Aadenosine receptor antagonists, ortheir combination, did not have any effect. However, under unrestricted access conditions caffeine and theadenosine A2Areceptor antagonist increased ethanol intake. After splitting animals into high, moderate and lowethanol consumers, caffeine (2.5–20.0 mg/kg) significantly increased ethanol consumption in moderate con-sumers with no effect on low or high consumers. In addition, after reintroducing ethanol access, caffeine(5.0 mg/kg) decreased ethanol consumption among moderate consumers. Thus, caffeine produced differenteffects on ethanol intake depending on the access condition and the baseline consumption of ethanol