Effects of self- and experimenter-administered cocaine on subsequent ethanol drinking in rhesus monkeys

Background One possible reason for the lack of FDA-approved pharmacotherapies to treat cocaine use disorder (CUD) is that, although cocaine is typically used in combination with alcohol, it is studied in isolation in preclinical studies. A better understanding of the cocaine-alcohol interactions that promote polysubstance use (PSU) will improve animal models of CUD and hasten pharmacotherapy development. We used a rhesus monkey model of cocaine-alcohol PSU to investigate one possible mechanism: that alcohol is used to mitigate negative effects associated with termination of cocaine use. Methods In 6 adult male rhesus monkeys, the relationship between self-administered cocaine intake and oral ethanol intake 2hours later was examined during self-administration of cocaine (0.0003-0.3mg/kg per injection, i.v.) under a fixed-ratio 30 schedule (FR30) or a progressive-ratio (PR) schedule. Next, ethanol consumption was measured 0-120minutes after experimenter-administered cocaine (0.3-1.7mg/kg, i.v.). Results Self-administered cocaine intake under both FR30 and PR schedules was unrelated to oral ethanol intakes 2hours later. When cocaine was administered non-contingently, cocaine decreased ethanol intake as well as intake of a non-alcoholic solution (n=4) in a time- and dose-dependent manner. Conclusions Taken together, the results do not provide evidence for cocaine-induced increases in ethanol consumption. By extension, the results do not support the hypothesis that cocaine users drink alcohol to counteract negative effects that occur after terminating use. This finding implies either that such effects do not exist or that such effects exist but are unaffected by ethanol.