A recent investigation of GABAA function in a genetically heterogenous cohort of alcohol dependent (AD) and alcohol-exposed control (CTL) subjects revealed no alteration in GABA-evoked current in directly differentiated, excitatory-enriched neurons following chronic alcohol treatment (Lieberman et al., 2018). The lack of GABA adaptation could be due to the absence of GABAergic signaling in the excitatory-enriched neural cultures, since three-week exposure to chronic ethanol significantly increased transcription levels of GABRA1 and GABRG2 in both AD and CTL groups. GABRD only showed a modest increase (24%) for the AD but not the CTL group (Lieberman et al., 2018), which is consistent with GABRD suggested as an AUD-candidate gene (Rodd et al., 2007). The comparison of differential effects of ethanol on human cells derived from healthy and alcohol dependent subjects illustrates how to use hiPSC-derived cells to study AUDs.
