Involvement of the GABA sub(A) Receptor in Age-Dependent Differences in Binge-Like Ethanol Intake

• Published in: Alcoholism, clinical and experimental research Vol. 40; no. 2; pp. 408 - 417
• Main Authors: Quoilin, Caroline, Boehm, Stephen L
• Format: Journal Article
• Language: English
• Published: 01.02.2016
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.12953

Background Binge alcohol (ethanol [EtOH]) drinking is common during adolescence, a time characterized by many behavioral and neurobiological changes. Among them, the GABA sub(A) 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 GABA sub(A) receptor agonists on binge-like EtOH intake in adolescent and adult mice using the Drinking-in-the-Dark model. Methods 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 GABA sub(A) agonist, were assessed in a first experiment. The second experiment tested for the more specific involvement of delta -containing extrasynaptic GABA sub(A) receptors through the administration of THIP (4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol). Results Adolescent mice consumed more EtOH than their adult counterparts. Following the administration of GABA sub(A) 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. Conclusions This study adds to the existing literature demonstrating the crucial role of the GABA sub(A) receptor in alcohol consumption. In addition, it suggests that age differences in the GABA sub(A) receptor modulation of binge alcohol drinking might be more dependent on extrasynaptic GABA sub(A) receptors. Using the drinking-in-the-dark procedure, this study investigated the role of GABAA receptors in binge-like ethanol intake in adolescent and adult mice. While muscimol, a full GABAA agonist, equally reduced ethanol consumption at both ages, age differences occurred following the administration of THIP, a selective drug for 8-containing extrasynaptic receptors. As such, adolescents were more sensitive to the suppressant effects of THIP, suggesting that age differences in the GABAA receptor modulation of binge alcohol drinking might depend more on extrasynaptic receptors.