Next, we aimed to gauge whether N40 and D40 AD-iNs respond differently to MOR activation following 5 min of acute (40 mM) ethanol application (Supplemental Fig. S3). To execute this, we employed a MOR-specific agonist DAMGO ([D-Ala 2, N-MePhe4, Gly-ol]-enkephalin) in combination with 40 mM ethanol, to study its role in modulating inhibitory synaptic output following ethanol exposure alone. DAMGO suppressed the ethanol-mediated increase in sIPSC frequency in both N40 and D40 AD-iNs (Supplemental Fig. S3A, B). However, the suppression of sIPSC frequency was more robust in D40 AD-iNs when compared to N40 iNs cells, following ethanol application (Supplemental Fig. S3B, **p ≤ 0.01). There was no difference observed in sIPSC amplitude following DAMGO application in either genotypes (Supplemental Fig. S3C). These data suggest a genotype-dependent regulation of MOR signaling following acute ethanol application.
