Because iPSC culture is costly and time consuming, we were limited to the examination of a single concentration of alcohol (50 mM), which we selected because it has been used for in vitro studies using rodent neurons examining the effects of alcohol on GABA receptor expression and function, and because we used this concentration in our previous study examining alcohol’s actions on NMDA receptors in iPSC-derived neural cell lines (Lieberman et al. 2012). The 50 mM concentration corresponds to a breath alcohol concentration of 0.24 g/dL, which is three times the legal driving limit of 0.08 in most U.S. states. Lower concentrations of alcohol (<10 mM) that are reached with social drinking have been shown to target extrasynaptic δ subunit-containing GABAA receptors (Sundstrom-Poromaa et al. 2002, Wei et al. 2004). Future studies could utilize iPSC-derived neural cells to examine the effects of low concentrations of alcohol, which may be more relevant to the initiation of drinking, and may help to elucidate cellular mechanisms important in the transition from social drinking to the development of an alcohol use disorder.
