GABRG1 has until recently been in the shadow of its neighbor, GABRA2, and has not been considered a prime candidate gene for alcoholism. In the rat, GABRG1 is expressed in only a few brain regions, primarily in the amygdala and all areas receiving innervation from the striatum including the substantia nigra (Pirker et al, 2000; Schwarzer et al, 2001). These are regions that are implicated in reward and addiction. The GABAA receptor subunit composition determines distinct pharmacological and electrophysiological properties. Studies have shown that γ1 subunits co-assemble with α2 subunits in vivo largely as α2β1 γ1 receptors (Whiting, 2003) that are much less responsive to the effects of benzodiazepines than receptors with the much more common γ2 subunit (Wafford et al, 1993). In contrast, the anxiolytic effects of benzodiazepines and barbiturates appear to be mediated in part by α2 subunits co-assembled with γ2 subunits (Dixon et al, 2008; Low et al, 2000). Thus it is possible that α2β1 γ1 receptors may be implicated in alcoholism vulnerability per se whereas variation in the more common receptors with co-assembled α2 and γ2 subunits may predispose to alcoholism mediated by anxiety.
