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

Abstract

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 twobottle 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.

Moderate Adolescent Ethanol Vapor Exposure and Acute Stress in Adulthood: Sex-Dependent Effects on Social Behavior and Ethanol Intake in Sprague–Dawley Rats

“…A similar decrease in anxiety-like behavior was observed using another adolescent vapor exposure paradigm (five two-hour exposures, BECs ~172 mg/dL) in both the light-dark box and elevated plus-maze [22]. Interestingly, sex differences have been repeatedly reported, with males showing more long-term deficits, especially relating to social anxiety-like behaviors, while females may be more vulnerable to increased ethanol intake in adulthood following adolescent ethanol exposure [17,[23][24][25][26]. Together, these studies suggest that the effects of adolescent ethanol exposure are quite variable, particularly at relatively high levels of ethanol exposure.…”