An Experimental Study to Evaluate the Role of Buprenorphine, Morphine, and Naltrexone in Animal Models of Depression

Buprenorphine demonstrated robust antidepressant-like activity in UCMS, likely mediated by KOR antagonism with contributions from MOR, delta-opioid, and nociceptin opioid peptide (NOP) receptors. Co-administration with naltrexone preserved efficacy while potentially reducing abuse liability. These findings highlight buprenorphine-based regimens as mechanistically novel candidates for further evaluation in treatment-resistant depression.