Sex and age differences in heavy binge drinking and its effects on alcohol responsivity following abstinence

Abstract

Binge drinking during adolescence may perturb the maturing neuroenvironment and increase susceptibility of developing an alcohol use disorder later in life. In the present series of experiments, we utilized a modified version of the drinking in the dark-multiple scheduled access (DID-MSA) procedure to study how heavy binge drinking during adolescence alters responsivity to ethanol later in adulthood. Adult and adolescent C57BL/6J (B6) and DBA/2J (D2) males and females were given access to a 20% ethanol solution for 3 hourly periods, each separated by 2h of free water access. B6 adults and adolescents consumed 2 to 3.5 g/kg ethanol an hour and displayed significant intoxication and binge-like blood ethanol concentrations. There was an interaction of sex and age, however, driven by high intakes in adult B6 females, who peaked at 11.01 g/kg. Adolescents of both sexes and adult males never consumed more than 9.3 g/kg. D2 mice consumed negligible amounts of alcohol and showed no evidence of intoxication. B6 mice were abstinent for one month and were retested on the balance beam 10 min following 1.75 g/kg ethanol challenge (20%v/v; i.p). They were also tested for changes in home cage locomotion immediately following the 1.75 g/kg dose (for 10 min prior to balance beam). Although there was no effect of age of exposure, all mice with a binge drinking history demonstrated a significantly dampened ataxic response to an ethanol challenge. Female mice that binge drank during adulthood showed a significantly augmented locomotor response to ethanol when compared to their water drinking controls. This alteration was not noted for males or for females that binge drank during adolescence. These results highlight the importance of biological sex, and its interaction with age, in the development of behavioral adaptation following binge drinking.