It is possible that we did not observe robust effects of alcohol exposure on either GABAA subunit gene expression or GABA-evoked currents due to deficits in neuroactive steroid signaling in iPSC-derived neural cultures. Exposure to alcohol stimulates the production of GABAA-receptor modulating neurosteroids (Morrow et al. 2001, Sanna et al. 2004, Morrow et al. 2006, Tokuda et al. 2011), which, in part, mediate the potentiating effects of alcohol at GABAA receptors in rodent brain slice preparations (Sanna et al. 2004). Prolonged exposure to neurosteroids produces GABAA subunit gene expression changes that mimic alcohol exposure, and can be blocked by the inhibition of neurosteroid biosynthesis with finasteride (Yu et al. 1996, Follesa et al. 2000, Follesa et al. 2004), suggesting that some of the effects of alcohol on GABAA receptor function and gene expression may be mediated through neurosteroids. Further, using brief applications of the synthetic neuroactive steroids gaboxadol and ganaxolone together with GABRD knock out mice Vashchinkina et al., (2012 and 2014) have shown that neurosteroid activation of GABRD receptors results in long-lasting glutamate receptor synaptic plasticity in ventral tegmental
