Repeated adolescent restraint stress alters ethanol intake, body weight gain, and glucocorticoid excretion in male and female BALB/cJ and C57BL/6J mice.

Alcohol use occurs in both men and women, yet preclinical alcohol research has historically focused on male rodents. Adolescent stress is a known risk factor for later alcohol misuse, but how stress history interacts with sex to influence intake remains unclear. To address this, we examined whether repeated adolescent restraint stress alters voluntary ethanol consumption in male and female BALB/cJ and C57BL/6J mice. Mice underwent 14 days of 2-h daily restraint beginning on postnatal day (PND) 37, followed by 4 weeks of binge-like ethanol drinking using the Drinking-in-the-Dark protocol starting on PND 53. Body weight and fecal corticosterone were measured to assess physiological adaptation and hypothalamic-pituitary-adrenal axis activity. Adolescent stress increased ethanol consumption in both strains, but with distinct temporal patterns. C57BL/6J mice showed a transient increase during the second week of drinking, whereas male BALB/cJ mice showed increased consumption during the fourth week. Stress delayed body weight gain in both strains, but recovery differed by strain and sex. Female C57BL/6J mice recovered by the final days of stress, whereas male and female BALB/cJ mice recovered within 2 weeks after stress ended. In contrast, male C57BL/6J mice did not recover. One week after stress cessation, fecal corticosterone remained elevated in stressed BALB/cJ mice, but not in C57BL/6J mice. These findings demonstrate that sex and genetic background shape physiological recovery from adolescent stress and subsequent ethanol consumption.