Female rats are more vulnerable to binge drinking behavior in an operant self-administration paradigm: implication for transition to alcohol use disorders

Abstract While binge drinking can significantly impact health negatively, it has become increasingly important to understand how sex differences contribute to this hazardous behavior, which may also serve as a risk factor for alcohol use disorder. We employed the binge drinking experimental model we developed previously to specifically analyze sex differences. Forty male and 40 female Long Evans rats were tested in the alcohol self-administration procedure, operationalized as alcohol responding in short daily session. We tested other parameters, including motivation, seeking, responses during cue omission sessions, withdrawal scores, and relapse after abstinence. We also conducted experiments to assess perseverance despite satiety. For the analysis we used first an unsupervised clustering approach using drinking speed and frequency of alcohol responses and then we analyzed our data by taking sex as the differentiating factor. Unbiased clustering analysis revealed four distinct groups: Fast Bingers, Bingers, Extreme Bingers and Low drinkers. Higher alcohol consumption and faster consumption speed correlated with elevated withdrawal scores. Sex-related differences were observed, with females outnumbering males in Extreme bingers. Females also exhibited higher alcohol-seeking behavior, relapse rates, and withdrawal scores. In addition, females exhibit lower sensitivity to devaluation in the satiety test. Our results suggest that females display greater vulnerability to cue-mediated alcohol-seeking behaviors and a more inflexible behavior. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research on binge drinking behaviors that is not only a hazardous behavior but may also be a critical factor in AUD vulnerability, particularly in females.