Ethanol self-administration reduced the efficacy of a behavioral intervention to decrease cocaine choice in socially...

In the clinical population, cocaine is frequently used sequentially or simultaneously with alcohol, and this pattern is linked to poorer treatment outcomes for cocaine use disorder (CUD). Yet, the impact of ethanol on cocaine reinforcement when non-drug alternatives are available remains unclear. In this study, we examined the effects of ethanol self-administration (1.5g/kg, one hour prior) on cocaine reinforcement under a concurrent cocaine vs. food choice (0.001-0.1mg/kg/injection) procedure in eight socially housed male and female cynomolgus monkeys. Daily sessions consisted of an initial 1hr access to either 1.5g/kg of a sweetened ethanol solution or a sweetened vehicle solution of corresponding volume. These solutions were available in the operant chamber. After the 1-hr fluid access, food (1.0-g food pellet) was available as an alternative to cocaine; only one cocaine dose was available per session. Cocaine choice increased in a dose-dependent manner and ethanol self-administration did not alter the potency of cocaine. To determine whether the reinforcing strength of cocaine was altered by co-use of ethanol, delays were added to the lowest preferred dose of cocaine. When monkeys were exposed to ethanol self-administration, they required longer delays to decrease cocaine choice, suggesting that ethanol increased the reinforcing strength of cocaine. These effects were consistent across sex and social rank. Together, these findings suggest that ethanol may diminish the effectiveness of interventions designed to shift behavior away from cocaine and towards non-drug alternatives. Modeling polysubstance use in preclinical studies will likely improve the likelihood that candidate treatments for CUD will translate successfully to the clinic.