Repeated, moderate footshock reduces the propensity to relapse to alcohol seeking in female, but not male, iP rats.

Persistent alcohol use despite negative consequences is a key feature of alcohol use disorder (AUD) and is typically assessed using punishment in animal models. This study examined relapse-like behavior in male and female alcohol-preferring iP rats following punishment-imposed voluntary abstinence to alcohol seeking. We focused on alcohol seeking in the punishment-associated environment after prolonged abstinence. Finally, we sought to understand the predictability of relapse-like behavior by examining AUD comorbidities, namely, anxiety-like behavior and the response to repeated, moderate punishment. We found no sex differences in operant self-administration of alcohol. However, we did find a reduced propensity to relapse in the punishment-associated environment in female rats following prolonged abstinence. Relapse propensity was associated with the response to punishment during operant training, but not prior anxiety-like behavior. Together these results highlight the importance of studying sex differences in relapse to alcohol seeking. In addition, the behavioral response to a negative consequence may be a predictor of relapse, particularly in females. Improving our understanding of the sexually dimorphic responses in alcohol seeking may be a powerful tool for designing personalized, or at least sex-specific, approaches to treatment and rehabilitation programs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).