an opioid agonist, MOR N40D allele iNs consistently exhibited stronger suppression, which suggests that this SNP causes a gain of MOR function. These data show altered opioid responsivity and/or dependence between human MOR genetic variants (Halikere et al., 2019). The current study found an altered ethanol response on GABAergic neurotransmission between MOR genetic variants that depends on the time and concentration of exposure (Figs. 4 and 5). Interestingly, our data indicate that MOR signaling is likely not involved in the ethanol sensitivity observed in AD-iNs. It is possible that ligand-independent MOR activity might contribute to the differences seen between MOR N40- and D40-harboring AD-iNs. However, a recent study looked at the impact of the opioid antagonist naltrexone on inhibitory synaptic transmission in AD-iNs and found no effect (Halikere et al., 2019). This suggests that, in the absence of ligand, MOR is not influencing synaptic output. Another possibility is the presence of iNs in our cultures that are capable of releasing endogenous opioids. We have briefly examined this but failed to detect any endogenous opioids in our cultures. These data may ultimately help predict altered ethanol sensitivity and/or dependence for individuals who carry MOR N40D allelic variants. Finally, opioid receptors have
