can potentially influence the phenotype. Our study employs isogenic stem cell lines, which allows us to specifically study the impact of MOR N40D, without known contributions from any differences in the genetic background or those that can be attributed to ethnicity (Halikere et al., 2019). Thus, the identification of differential sensitivities to acute and chronic ethanol for AD-iNs is interpreted as a direct consequence of only the MOR N40D variant. 2) The disease of addiction is a progressive process. Interactions with various neurotransmitter and neuromodulator systems promote the pharmacological effects of alcohol. Neuromodulators, such as endogenous opioids, play a pivotal role in the reinforcing and rewarding effects of alcohol, leading to addiction. Our study utilizes a homogenous population of GABAergic neurons, which allows us to probe the functional consequence of acute and chronic ethanol exposure on a relatively homogenous population of AD-iNs carrying MOR N40D genetic variants. This suggests that the MOR plays a role in the ethanol response independent of opioid binding and MOR activation. However, exogenous MOR-specific agonists can be supplied to the cultures, and MOR functionality can be directly probed in response to ethanol-mediated facilitation of GABAergic synaptic release. In this study, we observed a more robust
