The past decade has brought many advances in our understanding of ethanol’s acute and chronic actions mediated by gamma-aminobutyric acid type A (GABAA) receptors in the central nervous system (CNS). The field has uncovered the GABAergic mechanisms that underlie many of the behavioral effects of ethanol, including its anxiolytic, anticonvulsant, sedative-hypnotic, cognitive-impairing, and motor incoordinating actions. These mechanisms include direct and indirect effects on GABAA receptors as well as effects on GABA release and the synthesis and availability of endogenous neuroactive steroids. The effects of chronic ethanol exposure have also been more clearly elucidated in rodents, monkeys, and humans, and there is a better understanding of the intracellular mechanisms that mediate adaptations of GABAA receptors to ethanol. The purpose of this article is to highlight the advances of the past decade and to underscore new insights into the mechanisms of ethanol’s actions and adaptations, particularly for their therapeutic relevance in the development of medications to support recovery from ethanol dependence and treatment of alcoholism.
