From a neurobiological standpoint, genetic variation in the GABRG1 locus may influence the liability to AD through mechanisms of reward and/or drug responsivity. In the rat brain, the γ-1 subunit of the GABAA receptor, encoded by the GABRG1 gene, is expressed selectively in only a few regions such as the amygdala, striatum, and substantia nigra (Pirker et al., 2000); these regions in turn are often implicated in addiction and reward mechanisms. Pharmacological studies have shown that GABAA γ-1 receptors are associated with lower sensitivity to benzodiazepine antagonists (Khom et al., 2006). As such, it is plausible to hypothesize that functional polymorphisms in the GABRG1 leading to alterations γ-1 receptors may ultimately influence the risk to alcoholism by altering tolerance and reward pathways. A great deal of research is needed to more fully ascertain this putative genetic association and its mechanisms, yet from a theoretical and neurobiological point of view, the GABRG1 gene represents a plausible candidate gene for addiction phenotypes.
