Ethanol consumption prior to cocaine self-administration reduced vulnerability to cocaine reinforcement in socially subordinate female and male monkeys.

Rationale: Although ethanol consumption is ubiquitous among individuals who use cocaine, most preclinical work investigating factors that contribute to the development of problematic cocaine use do not incorporate ethanol into their experimental designs. Given that only a subset of individuals who try cocaine go on to develop a cocaine use disorder (CUD) research is needed to identify factors, such as ethanol consumption, that may influence vulnerability to cocaine reinforcement.

Objectives: Thus, this study aimed to determine how a history of ethanol self-administration and exposure immediately prior to the first experience with cocaine self-administration influenced the potency of cocaine to function as a reinforcer in socially housed male and female cynomolgus monkeys.

Methods: For these experiments, one group of monkeys (n = 7) was trained to self-administer up to 1.5 g/kg of ethanol prior to cocaine self-administration while another group of monkeys (n = 13) remained ethanol-naïve through the study. Acquisition of cocaine self-administration was studied in both groups of monkeys under a fixed-ratio schedule of reinforcement where ascending doses of cocaine were substituted for food pellets. Cocaine ED50 values from the ascending limb were examined statistically.

Results: The results showed that subordinate monkeys that self-administered ethanol prior to cocaine self-administration required higher cocaine doses to function as a reinforcer compared with subordinate monkeys not exposed to ethanol.

Conclusions: One possible explanation for this finding is that ethanol, due to its acute anxiolytic effects, mitigated the effect of chronic stress in subordinate monkeys and thereby blunted the reinforcing effects of initial cocaine exposure. Future research is needed to examine whether variables such as environmental enrichment or treatment with clinically effective anxiolytics in chronically stressed individuals can modify the initiation and continued use of cocaine.