Role of the treatment environment in the effects of aripiprazole on ethanol-induced behavioral sensitization and conditioned place preference in female mice

•Behavioral sensitization to ethanol (BSE) only occurred after a drug-free interval.•Repeated treatment with aripiprazole attenuated the expression of BSE.•The effects of aripiprazole on BSE did not depend on the treatment environment.•Aripiprazole prevented the reinstatement of ethanol-induced CPP.•Aripiprazole blocked CPP when given in the CPP apparatus, but not in the home-cage. Evidence suggests that aripiprazole, a partial dopamine D2 and serotonin 5-HT1A receptor agonist and 5-HT2A receptor antagonist, show significant efficacy in reducing alcohol use. We have previously demonstrated that treatment with aripiprazole blocked the reinstatement of cocaine-induced behavioral sensitization in a context-dependent manner, suggesting that the treatment environment may modulate the therapeutic effects of aripiprazole. The present study aimed to evaluate the effects of treatment with aripiprazole on ethanol-induced behavioral sensitization and conditioned place preference in female mice, and the role of the treatment environment in those effects. Adult female mice were either sensitized with ethanol injections in the open-field apparatus, or conditioned with ethanol in the conditioned place preference (CPP) apparatus. Animals were then treated with vehicle or 0.1 mg/kg aripiprazole paired to the test environment (open-field or CPP apparatus) or not (home-cage treatments) for 4 alternate days, and the subsequent expression of behavioral sensitization or CPP to ethanol was evaluated during or following an ethanol re-exposure, respectively. Repeated treatment with aripiprazole attenuated the expression of ethanol-induced behavioral sensitization regardless of the treatment environment. Treatment with aripiprazole was only effective at preventing the reinstatement of ethanol-induced CPP when paired with the ethanol-associated environment, but not when administered in the home-cage. The present findings corroborate previous studies suggesting the effectiveness of aripiprazole for the treatment of alcohol use disorder. Our results also point to an important role of the treatment environment in the therapeutic effects of aripiprazole in rodent models of ethanol abuse.