Role of GABAA receptors in the actions of alcohol and in alcoholism: recent advances.

Abstract

Brain GABAergic mechanisms are interesting with regard to their role in the actions of ethanol. The present review summarizes some of the more recent studies, most of them biochemical, electrophysiological and pharmacogenetic. While there is still a number of controversies, e.g. regarding the molecular mechanisms of ethanol enhancement of GABAA receptor-mediated anion flux and the effects of chronic alcohol administration on the receptors in experimental animals and man, there is a substantial body of evidence supporting the involvement of these mechanisms in many behavioural actions of ethanol. Two recent findings warrant further molecular biological studies on the interaction between ethanol and the GABAA receptor, and the extension of the studies to human alcoholics: first, the effects of ethanol on the GABAA receptor are dependent on a specific gamma 2 subunit with an additional phosphorylation site; second, genetically enhanced sensitivity to the motor-impairing effect of moderate ethanol doses has a likely biological basis in a single-nucleotide mutation in a cerebellum-specific GABAA receptor subunit. Further studies are also needed to establish the role of GABAergic mechanisms in alcohol misuse and addiction.