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µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice
Khalin E Nisbett1,2,3, Leandro F Vendruscolo4, George F Koob5
1Graduate Program in Neuroscience, Graduate College, University of Illinois Chicago, Chicago, IL, 60607, USA. kay.nisbett@nih.gov.
Translational Psychiatry
|February 27, 2024
Summary
Oxytocin reduces anxiety-like behavior in mice, an effect enhanced by blocking mu-opioid receptors but not kappa-opioid receptors. This suggests endogenous opioids modulate oxytocin
Area of Science:
- Neuroscience
- Behavioral Science
- Pharmacology
Background:
- Mood and anxiety disorders are significant global health burdens.
- Neuropeptides like oxytocin and opioids are crucial for emotion regulation.
- The interaction between opioid and oxytocin systems in emotion regulation is not fully understood.
Purpose of the Study:
- To investigate the interaction between the endogenous opioid system and the oxytocin system in regulating anxiety- and depression-like behaviors in mice.
- To test the hypothesis that opioid receptor blockade inhibits the effects of oxytocin.
Main Methods:
- Mice were administered naloxone (a mu-opioid receptor antagonist) followed by oxytocin.
- Anxiety-like behavior was assessed using the elevated zero maze.
- Depression-like behavior was assessed using the tail suspension test.
- Selective antagonists for mu- and kappa-opioid receptors were used to further elucidate the mechanisms.
Main Results:
- Contrary to the hypothesis, naloxone potentiated the anxiolytic-like effect of oxytocin.
- Mu-opioid receptor blockade enhanced oxytocin's anxiolytic-like effect.
- Kappa-opioid receptor blockade inhibited oxytocin's anxiolytic-like effect.
- Neither mu- nor kappa-opioid receptor blockade affected the antidepressant-like effect of oxytocin.
Conclusions:
- The endogenous opioid system interacts with the oxytocin system to modulate anxiety-like behavior.
- Specifically, mu-opioid receptor activity appears necessary for oxytocin's antidepressant-like effects, while kappa-opioid receptor activity opposes oxytocin's anxiolytic-like effects.
- These findings have potential implications for understanding and treating mood and anxiety disorders.
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