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

Autor: Nisbett KE; Graduate Program in Neuroscience, Graduate College, University of Illinois Chicago, Chicago, IL, 60607, USA. kay.nisbett@nih.gov.; Stress & Addiction Neuroscience Unit, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, 21224, USA. kay.nisbett@nih.gov.; Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224, USA. kay.nisbett@nih.gov., Vendruscolo LF; Stress & Addiction Neuroscience Unit, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, 21224, USA., Koob GF; Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224, USA.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Feb 28; Vol. 14 (1), pp. 125. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1038/s41398-024-02830-1
Abstrakt: 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.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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