Among the 12 GABAA genes expressed in the DRN, 8 GABAA subunits showed reduced expression. Two subunits, Gabra6 and Gabrd, showed >4-fold increases. Thus, the balance of GABAA subunits was significantly altered, suggesting altered local inhibitory regulation within the DRN. The Gabrd subunit is found in extrasynaptic GABAA receptors composed primarily of α4 or α6 subunits along with β subunits (Lovinger and Roberto, 2013), which generate tonic inhibitory conductance that results in spontaneous low firing rates (Hanchar et al., 2005). These receptors are sensitive to ethanol, which potentiates this tonic current in a protein kinase C delta dependent manner (Lovinger and Roberto, 2013). Prkcd is also increased 2.4 fold. Gad1 (encoding glutamate decarboxylase 1, a rate-limiting enzyme for GABA synthesis) showed significant increases in expression following binge-like drinking; polymorphisms in Gad1 are associated with age of onset for alcohol dependence and initial alcohol sensitivity (Kuo et al., 2009).
