Given the implication of α2-containing GABAA receptor (GABAA-R) as one of the possible genetic links in alcoholism and its relatively high expression in many brain regions, it is important to determine the role of α2-containing GABAA-Rs in the behavioral actions of ethanol. In the present study, Blednov et al. used α2 knockin mice to test the hypothesis that α2-containing GABAA-Rs mediate specific behavioral responses to ethanol. Using α2 S270H/L277A ethanol-insensitive mutant GABAA-R knockin mice, it was demonstrated that these mutant mice did not develop the typical conditioned taste aversion in response to ethanol, showed complete loss of the motor stimulant effects of ethanol, and increased ethanol-induced hypnosis but showed no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the á2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism and may explain the association of polymorphisms in Gabra2 with alcoholism.
See article at J Pharmacol Exp Ther 2011, 336:145–154.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics