It is unclear whether GABAA receptors composed of the α2β2γ3 subunit combination exist in vivo in areas likely to be involved in alcohol-related phenotypes or predisposition to alcoholism. However based on in situ hybridization and immunocytochemistry studies it is likely that these subunit proteins co-localize in several brain regions which may be important in observed alcohol related phenotypes such as cortex and mesolimbic areas (reward pathways). The α2 subunit is found in 35% of GABAA receptors and in high concentrations in cortex, striatum, nucleus accumbens, septum, dentate gyrus and amygdala and hypothalamus. The γ3 subunit is less abundant but enriched in some regions which could contribute to risk for alcoholism including cortex, basal nuclei and hippocampus. The β2 subunit has not been linked to alcoholism but is the most abundant β isoform in mature brain. It is also important to point out that although our study has demonstrated differences in response to ethanol based on this subunit combination all 3 subunits may not be required to see similar functional changes.
