Adolescent binge drinking in male Wistar rats increases ethanol consumption and reduces intoxication sensitivity in early adulthood without affecting withdrawal

Background: Early adolescent ethanol exposure increases the risk of developing an alcohol use disorder. The mechanisms underlying this relationship may involve early ethanol exposure influencing anxiety or altering ethanol sensitivity. Objectives: To examine how adolescent binge drinking impacts sensitivity to ethanol intoxication, withdrawal symptoms, anxiety, compulsive behaviors, and ethanol intake in adulthood. Methods: Thirty-seven male Wistar rats self-administered ethanol during adolescence [postnatal days (PD) 27-45] or were housed under control conditions. In adulthood, the rats received intragastric intubations to simulate heavy alcohol (PDs 61-65, 3 daily doses of 0.0 or 1.5 g/kg) exposure. Intoxication and withdrawal symptoms were assessed (PDs 61-70), along with compulsive behaviors (marble burying test, PD68) and anxiety-related behaviors (light-dark box and elevated plus maze tests, PDs 69-70). Two-bottle choice tests provided measures of ethanol intake (PDs 75-87). Results: Adolescent binge exposure increased ethanol consumption in adulthood (p < .001; eta 2 = 0.51), with binge-exposed rats drinking 4.5-6.5 g/kg/day vs. 2 g/kg/day in controls. Binge-exposed rats exhibited reduced sensitivity to ethanol intoxication (p < .05; eta 2 = 0.17). Withdrawal symptoms were significantly greater (p < .005; eta 2 = 0.36) in rats exposed to alcohol during adulthood compared to controls, regardless of binge ethanol exposure. Anxiety or compulsive behaviors were unaffected by binge ethanol. Conclusions: Adolescent binge drinking led, in male rats, to significant increases in ethanol intake and reduced sensitivity to intoxication in adulthood. These findings suggest that early ethanol exposure results in decreased ethanol sensitivity, potentially increasing the likelihood of ethanol use. Adolescent binge drinking is a key vulnerability factor, and interventions should target this behavior.