µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

Khalin E. Nisbett, M.S.

Hot Off the Press – March 26, 2024

Published in Translational Psychiatry by Khalin Nisbett, Leandro Vendruscolo and George Koob from the NIDA IRP Stress & Addiction Neuroscience Unit and Neurobiology of Addiction Section.

Summary

Nisbett et al. discovered that the anxiolytic-like (anxiety-reducing) effect of oxytocin can be modulated by the endogenous opioid system. We demonstrated that blocking m-opioid receptors (receptors for endorphins) can amplify the anxiolytic-like effect of oxytocin. Whereas blocking k-opioid receptors (receptors for dynorphins) can dampen the anxiolytic-like effect of oxytocin. These findings suggest that opioids (natural or synthetic) can interact with the oxytocin system to control emotion-related behaviors. These findings may have implications for novel therapeutic approaches for substance use disorders since naltrexone is an FDA-approved medication to treat opioid and alcohol use disorder and oxytocin is currently being explored as a treatment for alcohol use (ClinicalTrials.gov Identifier: NCT03878316) and other mood and anxiety disorders.

Publication Information

Nisbett, Khalin E; Vendruscolo, Leandro F; Koob, George F

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice Journal Article

In: Transl Psychiatry, vol. 14, no. 1, pp. 125, 2024, ISSN: 2158-3188.

Abstract | Links

@article{pmid38413576,

title = {µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice},

author = {Khalin E Nisbett and Leandro F Vendruscolo and George F Koob},

url = {https://pubmed.ncbi.nlm.nih.gov/38413576/},

doi = {10.1038/s41398-024-02830-1},

issn = {2158-3188},

year  = {2024},

date = {2024-02-01},

urldate = {2024-02-01},

journal = {Transl Psychiatry},

volume = {14},

number = {1},

pages = {125},

abstract = {Mood and anxiety disorders are leading causes of disability worldwide and are major contributors to the global burden of diseases. Neuropeptides, such as oxytocin and opioid peptides, are important for emotion regulation. Previous studies have demonstrated that oxytocin reduced depression- and anxiety-like behavior in male and female mice, and opioid receptor activation reduced depression-like behavior. However, it remains unclear whether the endogenous opioid system interacts with the oxytocin system to facilitate emotion regulation in male and female mice. We hypothesized that opioid receptor blockade would inhibit the anxiolytic- and antidepressant-like effects of oxytocin. In this study, we systemically administered naloxone, a preferential μ-opioid receptor antagonist, and then intracerebroventricularly administered oxytocin. We then tested mice on the elevated zero maze and the tail suspension tests, respective tests of anxiety- and depression-like behavior. Contrary to our initial hypothesis, naloxone potentiated the anxiolytic-like, but not the antidepressant-like, effect of oxytocin. Using a selective μ-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, and a selective κ-opioid receptor antagonist, norbinaltorphimine, we demonstrate that μ-opioid receptor blockade potentiated the anxiolytic-like effect of oxytocin, whereas κ-opioid receptor blockade inhibited the oxytocin-induced anxiolytic-like effects. The present results suggest that endogenous opioids can regulate the oxytocin system to modulate anxiety-like behavior. Potential clinical implications of these findings are discussed.},

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pubstate = {published},

tppubtype = {article}

}