Why and how GABRA2 might affect the brain's reward system is uncertain. The variation in GABRA2 that has been associated with alcoholism occurs in non-coding regions of the gene, and presumably affects gene expression. In that respect, differential expression of GABA-A α2 subunits has the potential to affect GABA currents (inhibitory neurotransmission) both alone and in the presence of alcohol (Hurley et al., 2009). After repeated pairing between alcohol's pharmacologic effects and its other closely linked sensory properties, such as smell and taste, it is conceivable that differential GABA signaling could alter reward system responses to these classically conditioned cues. In similar vein of thought, Hemby et al (2006) showed that chronic ethanol exposure in primates altered GABA-A α2 subunit mRNA expression in orbitofrontal cortex, which these authors theorized could play a role in altering the perception of and response to stimulus salience. On the other hand, GABRA2 variation could affect broader parameters, such as personality and behavioral inhibition (Dick et al., 2006; Lind et al., 2008), particularly if the GABRA2 association with alcohol disorders is more prominent in polysubstance
