Involvement of the GABAA Receptor in Age-Dependent Differences in Binge-Like Ethanol Intake

Binge alcohol (ethanol [EtOH]) drinking is common during adolescence, a time characterized by many behavioral and neurobiological changes. Among them, the GABAA receptor system undergoes substantial modifications, including changes in the density, distribution, and subunit composition of the receptor. Based on its demonstrated role in EtOH consumption, this study aimed to investigate the effects of 2 different GABAA receptor agonists on binge-like EtOH intake in adolescent and adult mice using the Drinking-in-the-Dark model.

Three hours into their dark cycle, adolescent (postnatal day 28 [P28]) and adult (P63) male C57BL/6J mice were given daily access to 20% EtOH for 2 hours during 8 consecutive days. Immediately before the access on day 8, mice (P35 and P70) were systemically injected with 1 of 2 different GABAergic drugs. The effects of muscimol, a full GABAA agonist, were assessed in a first experiment. The second experiment tested for the more specific involvement of δ-containing extrasynaptic GABAA receptors through the administration of THIP (4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol).

Adolescent mice consumed more EtOH than their adult counterparts. Following the administration of GABAA agonists, levels of EtOH intake were reduced at both ages. However, age-dependent differences were revealed following the administration of THIP, with adolescents exhibiting greater sensitivity to its suppressant effects, especially during the first 30 minutes of binge EtOH access.

This study adds to the existing literature demonstrating the crucial role of the GABAA receptor in alcohol consumption. In addition, it suggests that age differences in the GABAA receptor modulation of binge alcohol drinking might be more dependent on extrasynaptic GABAA receptors.