ArticleCureus2025
An Experimental Study to Evaluate the Role of Buprenorphine, Morphine, and Naltrexone in Animal Models of Depression.
Article in Cureus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
backgroundOpioids have a long-standing history of being used for the treatment of mood disorders, with recent attention directed towards kappa opioid receptors (KOR) for antidepressant drug development. Activation of KOR produces dysphoria and anhedonia, whereas antagonism confers antidepressant-like effects. Buprenorphine, a partial mu-opioid receptor (MOR) agonist and KOR antagonist, exhibits antidepressant properties but carries a risk of abuse liability. Naltrexone, a non-selective opioid antagonist, may mitigate this risk while preserving KOR antagonism. This study evaluated the antidepressant-like effects of buprenorphine, morphine, and naltrexone individually, as well as the combination of buprenorphine and morphine with naltrexone, in validated models of depression. Experimental approach: Male mice were subjected to unpredictable chronic mild stress (UCMS) for four weeks. Following stress induction, drug treatments were administered for 14 days: buprenorphine (1 mg/kg), naltrexone (1 mg/kg), morphine (5 mg/kg), their combinations, or fluoxetine (10 mg/kg) as a reference. Behavioral assessments included the Sucrose Preference Test (SPT), Open Field Test (OFT), Forced Swim Test (FST), and Tail Suspension Test (TST).
resultsUCMS induced anhedonia and behavioral suppression, confirmed by reduced sucrose consumption, locomotor activity, and increased immobility. Buprenorphine significantly reversed these effects across all assays, with efficacy comparable to fluoxetine. The buprenorphine-naltrexone combination also produced significant antidepressant-like effects, though slightly less pronounced than buprenorphine alone. Morphine and naltrexone showed partial or inconsistent effects.
conclusionBuprenorphine 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.
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