Adolescent intermittent ethanol exposure induces sex-dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice

With alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and motor behavior. Adolescents report higher rates of binge drinking compared to adults. Accompanying increased binge drinking rates, adolescents are more prone to substance use disorder (SUD) during adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long-lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence and in young adulthood. The present set of experiments were divided into four stages: (1) chronic intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using an intermittent vapor inhalation model with repeated binge pattern ethanol exposure from postnatal day (PND) 28-42. Following this exposure, mice underwent abstinence from PND 43-49 (Experiment 1) and PND 43-69 (Experiment 2). Beginning on PND 49-76 (Experiment 1) or PND 70-97 (Experiment 2), mice were assessed for intermittent voluntary ethanol consumption using a two-bottle drinking procedure over 28 days. Male mice that were exposed to ethanol during adolescence showed increased ethanol consumption during later adolescence (Experiment 1) and in adulthood (Experiment 2), while the females showed decreased ethanol consumption. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field and anxiety-like behavior. These data highlight sex-dependent vulnerability to developing substance use disorders in adulthood.