OUD (Fig. 3e), accompanied by downregulation of MAF, EST1, ETV1, and PRRX1 modules in D1/D2 hybrid MSNs (FDR < 0.043), each of which are implicated in neuronal stress76,77. Notably, BACH1, BCL11A, and PRRX1 have downstream targets with concordant differential expression in OUD (e.g., FOXP2, POUF3, PTPRD, RAB31, RCBTB2; Fig. 3e), indicating coordinated changes in striatal gene networks implicated in neuronal stress associated with opioid addiction. Additional findings included modules for NFATC2 and RXRG (FDR < 0.042; Fig. 3e). Both nuclear factor of activated T-cell C2 (NFATC2) and the retinoid X receptor gamma (RXRG) of the RXR family of receptors link changes in neuronal activity associated with addictive drugs to processes involved in neuroprotection, neurodegeneration78,79 and reward-related behaviors49,80.
