Quoilin Caroline, Boehm Stephen L
Addiction Neuroscience, Department of Psychology, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana.
Alcohol Clin Exp Res. 2016 Feb;40(2):408-17. doi: 10.1111/acer.12953. Epub 2016 Feb 2.
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.
青少年时期酗酒（饮用乙醇[EtOH]）的现象很常见，这一时期的特点是行为和神经生物学发生诸多变化。其中，γ-氨基丁酸A（GABAA）受体系统会发生显著改变，包括受体密度、分布和亚基组成的变化。基于其在乙醇摄入方面已被证实的作用，本研究旨在使用黑暗环境下饮水模型，探究两种不同的GABAA受体激动剂对青少年和成年小鼠暴饮样乙醇摄入量的影响。
在黑暗周期的第3小时，对青春期（出生后第28天[P28]）和成年（P63）雄性C57BL/6J小鼠，连续8天每天给予2小时的20%乙醇。在第8天给药前，对小鼠（P35和P70）进行两种不同的GABA能药物之一的全身注射。在第一个实验中评估了完全GABAA激动剂蝇蕈醇的作用。第二个实验通过给予4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP），测试含δ的突触外GABAA受体的更具体参与情况。
青春期小鼠比成年小鼠摄入更多的乙醇。给予GABAA激动剂后，两个年龄段的乙醇摄入量均降低。然而，给予THIP后发现了年龄依赖性差异，青少年对其抑制作用表现出更高的敏感性，尤其是在暴饮乙醇的前30分钟。
本研究补充了现有文献，证明了GABAA受体在酒精消费中的关键作用。此外，研究表明GABAA受体对暴饮酒精的调节存在年龄差异，可能更多地依赖于突触外GABAA受体。
