In summary, we utilized human iPSC-derived neural cell lines from CTL and AD donor subjects and found that chronic treatment with 50 mM alcohol increased the expression of α1 (GABRA1) and γ2 (GABRG2) subunit mRNA in both groups of neural cell lines, while expression of δ (GABRD) subunit mRNA was increased only in AD cell lines. Acute and chronic alcohol exposure had no effect on GABA-evoked currents examined via whole cell patch-clamp electrophysiology. This work supports the application of iPSCs to the study of alcohol use disorder, but suggests that future work should employ additional neural differentiation protocols that may generate more alcohol-responsive neural cell types to better elucidate molecular phenotypes that differentiate CTL- and AD-derived cell cultures. Additional evaluation of neural media supplements, including neurosteroid precursors, may help to improve the utility of in vitro cultures in recapitulating the in vivo milieu.
