TY - JOUR T1 - Caffeine Increases the Reinforcing Efficacy of Alcohol, an Effect that is Independent of Dopamine D<sub>2</sub> Receptor Function JF - bioRxiv DO - 10.1101/2020.09.04.283465 SP - 2020.09.04.283465 AU - Sarah E. Holstein AU - Gillian A. Barkell AU - Megan R. Young Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/09/08/2020.09.04.283465.abstract N2 - The rising popularity of alcohol mixed with energy drinks (AmEDs) has become a significant public health concern, with AmED users reporting higher levels of alcohol intake than non-AmED users. One mechanism proposed to explain heightened levels of alcohol intake in AmED users is that the high levels of caffeine found in energy drinks may increase the reinforcing properties of alcohol, an effect which may be dependent on interactions between adenosine signaling pathways and the dopamine D2 receptor. Therefore, the purpose of the current study was to confirm whether caffeine increases the reinforcing efficacy of alcohol using both fixed ratio (FR) and progressive ratio (PR) designs, and to investigate a potential role of the dopamine D2 receptor in caffeine’s reinforcement-enhancing effects. Male Long Evans rats were trained to self-administer a sweetened alcohol or sucrose solution on an FR2 schedule of reinforcement. Pretreatment with caffeine (5-10 mg/kg) significantly increased operant responding for the sweetened alcohol reinforcer, but not sucrose. PR tests of motivation for alcohol or sucrose likewise confirmed a caffeine-dependent increase in motivation for a sweetened alcohol solution, but not sucrose. However, the D2 receptor antagonist eticlopride did not block the reinforcementenhancing effects of caffeine using either an FR or PR schedule of reinforcement. Taken together, these results support the hypothesis that caffeine increases the reinforcing efficacy of alcohol, which may explain caffeine-induced increases in alcohol intake. However, the reinforcement-enhancing effects of caffeine appear to be independent of D2 receptor function.Competing Interest StatementThe authors have declared no competing interest. ER -