Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

Abstract

Introduction Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol) on conditioned taste aversion, ataxia and locomotor activity after repeated exposure. Methods Four groups of mice were exposed by oral gavage twice daily to vehicle, ethanol (4 g/kg), caffeine (15 mg/kg), or the ethanol/caffeine combination. Conditioned taste aversion to saccharin and ataxia in the parallel rod task were evaluated after 8 or 16 gavages, respectively, using ethanol (1–3 g/kg) or ethanol/caffeine (3mg/kg + 2 g/kg) challenges. In addition, locomotor activity was evaluated initially and after repeated exposure to oral gavage of these drugs and doses. Results Repeated oral gavage of ethanol produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/ethanol combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated ethanol exposure, there was significant tolerance to ethanol in the conditioned taste aversion and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced ethanol-induced conditioned taste aversion. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/ethanol combination and appeared to reduce the ataxic response to high doses of ethanol. Conclusion The data support the general hypothesis that repeated exposure to caffeine influences the response to ethanol. Together with previously published work, these data indicate that caffeine influences some ethanol-related behaviors, notably locomotion and ataxia, but appears not to influence the expression of conditioned behaviors.

Desire to Drink Alcohol is Enhanced with High Caffeine Energy Drink Mixers

“…Thus, the risks of drinking alcohol may be higher with consumption of AmED when compared to alcohol alone because the perceived stimulation is enhanced with an energy drink mixer. Given the importance of drug‐induced stimulation, it is notable that findings from several animal studies from different laboratories have reported that locomotor stimulation changes are enhanced for alcohol caffeine combinations when compared to either drug alone (Fritz et al., ; Hilbert et al., ; May et al., ). In one study, it was observed that binge consumption of alcohol by both adolescent and adult mice increased with caffeine, but only the adolescent mice exhibited robust locomotor stimulant responses to alcohol caffeine combinations (Fritz et al., ).…”

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

“…Recent experiments in mice have provided strong evidence for this hypothesis, showing that combination of caffeine and alcohol produce a stronger locomotor activity than either drug administered alone (Hilbert et al, 2013). The same research group recently reported that when given by oral gavage, repeated co-exposure to alcohol and caffeine produces a much larger effect than repeated exposure to either drug alone (May et al 2015). Under conditions of chronic alcohol intake (alcohol use disorder), in contrast to the acute situation, there is a reduced adenosine tone.…”

Red Bull® energy drink increases consumption of higher concentrations of alcohol

“…In contrast, most animal studies have investigated the health impact of mixing alcohol with the believed key psychoactive component of energy drinks, caffeine. For instance, it has been demonstrated in mice that alcohol mixed with caffeine causes an approximately fourfold increase in locomotion compared with orally administered alcohol or caffeine alone (May, Haun, & Griffin ). Similar locomotor results were recently observed in adolescent mice when they were allowed to voluntarily consume alcohol, caffeine or its combination in a limited‐access binge‐like alcohol drinking paradigm (Fritz et al .…”