ROLE OF GABA(A) RECEPTORS IN THE ACTIONS OF ALCOHOL AND IN ALCOHOLISM- RECENT ADVANCES

Brain GABAergic mechanisms are interesting with regard to their role i n the actions of ethanol. The present review summarizes some of the mo re 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 GABA(A) r eceptor-mediated anion flux and the effects of chronic alcohol adminis tration on the receptors in experimental animals and man, there is a s ubstantial body of evidence supporting the involvement of these mechan isms in many behavioural actions of ethanol. Two recent findings warra nt further molecular biological studies on die interaction between eth anol and the GABA(A) receptor, and the extension of the studies to hum an alcoholics: first, the effects of ethanol on the GABA(A) receptor a re dependent on a specific gamma2 subunit with an additional phosphory lation site; second, genetically enhanced sensitivity to the motor-imp airing effect of moderate ethanol doses has a likely biological basis in a single-nucleotide mutation in a cerebellum-specific GABA(A) recep tor subunit. Further studies are also needed to establish the role of GABAergic mechanisms in alcohol misuse and addiction.