In addition to the finding of direct activation of GIRK channels by alcohol, multiple animal studies have implicated GIRK channels, particularly GIRK2 and GIRK3 subunits, in alcohol abuse, as well as in psychostimulant addiction [19, 42]. In vivo studies with GIRK2 KO and GIRK2 weaver mice showed loss of ethanol-induced behaviors, such as anxiolytic and withdrawal effects [49], as well as analgesic effects [11, 50, 51]. GIRK2 KO mice did not develop a conditioned place preference for ethanol, exhibiting less sensitivity to its motivational effects [52]. GIRK3 KO mice, on the other hand, displayed conditioned place preference for ethanol [53] and enhanced ethanol binge drinking [19]. The activation of GIRK channels by alcohol and their demonstrated role in alcohol-related behaviors highlighted GIRK channels as a potential target for the study and treatment of alcohol abuse.
