Adolescent social isolation increases binge-like alcohol drinking in male but not female high-alcohol-preferring mice.

Aims: This study examined how adolescent social isolation affects adult binge-like alcohol drinking and stress-axis function, via basal levels of circulating corticosterone (CORT), in male and female mice with a genetic predisposition toward high alcohol preference (HAP).

Methods: Male and female HAP2 mice were randomly assigned to a group-housed or social isolation (ISO) group. Social isolation began at postnatal Days 40-42 and lasted for 21 days prior to assessment of binge-like alcohol drinking using a 4-day drinking-in-the-dark (DID) procedure. Blood samples to assess basal CORT were taken 6 days after social isolation ended and 24 h before DID started, and again 60 h after DID ended, during the light portion of the light cycle.

Results: Adolescent social isolation increased adult binge-like alcohol drinking in male but not female mice. All groups showed significantly lower CORT after DID compared to before DID. Pearson bivariate correlation coefficients between the first 2 h of grams-per-kilogram alcohol intake on Day 4 and CORT levels indicated a significant positive correlation in ISO males only after DID and negative correlations in ISO females before and after DID.

Conclusions: These findings demonstrate that adolescent social isolation increased binge-like alcohol drinking in male but not female adult HAP2 mice. Stress-axis adaptations in male HAP2 mice may be associated with the social-isolation-induced increase in binge-like alcohol drinking.