Ethanol self-administration prior to cocaine self-administration reduces sensitivity to cocaine reinforcement in socially housed monkeys.

Co-use of alcohol is highly prevalent among individuals who use cocaine. However, the behavioral mechanisms underlying co-use are not fully characterized. Thus, this study aimed to examine how ethanol (EtOH) self-administration prior to cocaine self-administration influenced the maintenance of cocaine self-administration in socially housed male (n = 4) and female (n = 4) cynomolgus monkeys responding under a fixed-ratio schedule of reinforcement. For these experiments, food (1.0 g flavored pellets) and cocaine dose-response curves (0.001-0.3 mg/kg) were determined when monkeys had access to 1.5 g/kg of a sweetened EtOH solution or an equal volume of a sweetened vehicle solution for one hour prior to cocaine self-administration. EtOH and the sweetened vehicle were readily self-administered by all monkeys, and consumption did not affect fixed-ratio food-maintained responding. When cocaine was studied, EtOH significantly decreased the potency of cocaine to function as a reinforcer relative to when the sweetened vehicle was self-administered. This relationship also appeared dose-dependent such that monkeys that drank more EtOH prior to the session had greater rightward shifts in the cocaine dose-response curve. Neither sex nor social rank influenced these outcomes. These data may suggest that EtOH decreased the reinforcing effects of cocaine, and/or attenuated the discriminative stimulus effects of cocaine. Future research is needed to examine how EtOH may modify cocaine use in the presence of a nondrug alternative reinforcer and to evaluate whether interventions aimed at reducing drug use are less effective in the context of co-use. SIGNIFICANCE STATEMENT: Cocaine users commonly report co-using alcohol simultaneously or in close succession. The present study found that ethanol (EtOH) self-administration prior to cocaine self-administration decreased the potency of cocaine to function as a reinforcer in nonhuman primates. These findings suggest that EtOH may decrease the effects of cocaine, and although not directly assessed in this study, EtOH may be used in combination with cocaine to mitigate the negative effects associated with cocaine use.