mRNA in AD neural cell lines, suggests that the regulation of the δ subunit may be relevant to the pathophysiology of alcohol use disorder. Because iPSCs reflect the donor subject’s genetic background, we may have seen an increase in GABRD in AD lines due to AD-derived neural cultures harboring a greater number of risk-associated genetic variants related to the regulation of GABRD expression than CTLs. Further studies are needed to elucidate the underlying genetic contributions of changes in GABRD regulation following alcohol exposure and to identify mechanisms linking the expression of GABRD to electrophysiological and behavioral outcomes. In this regard, it is noteworthy that GABRD has been implicated as an alcohol use disorder candidate gene (Rodd et al. 2007) and GABRD knockout mice show alcohol-related behavioral phenotypes, including reduced voluntary alcohol consumption and alcohol preference (Mihalek et al. 2001). Furthermore, pharmacological modulation of δ-containing GABAA receptors induced glutamate receptor plasticity on dopamine neurons in the ventral tegmental area suggesting that modulation of δ-containing GABAA receptors may be sufficient to induce the synaptic plasticity in this region that is commonly observed following administration of drugs of abuse (Vashchinkina et al. 2012, Vashchinkina et al. 2014).
