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 area dopamine neurons, including changes in AMPA/NMDA glutamate signaling ratios similar to those induced by acute alcohol exposure, further implicating endogenous neuroactive steroids in the neuroplastic effects of alcohol. Therefore, we may not have observed a robust effect of alcohol on GABAA receptor expression or function because our iPSC neural culture system may lack endogenous neurosteroids or neurosteroid precursors necessary to fully manifest alcohol’s effects. Future work could address this by examining changes in GABAA receptor gene expression following chronic treatment with neurosteroids or by examining the effect of alcohol in cultures containing neuronal media supplemented with upstream precursors for neurosteroid synthesis.
