ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder–Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial

Zimmermann, Sina; Thomas, Benjamin; Krisam, Johannes; Limprecht, Ronald; Klose, Christina; Stenger, Manuel; Pourbaix, Madeleine; Ries, Marcel; Vollstädt‐Klein, Sabine; Koopmann, Anne; Lenz, Bernd; Kiefer, Falk; Bach, Patrick

doi:10.1136/bmjopen-2021-059672

Cited by 2 publications

(1 citation statement)

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“…This is particularly important given the need for new pharmacotherapeutics for the treatment of psychiatric disorders, including substance use disorders [ 97 ]. Of interest would be clinical trials that are designed to investigate the combined effects of oxytocin and naltrexone [ 98 ].…”

Section: Discussionmentioning

confidence: 99%

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

Nisbett,

Vendruscolo,

Koob

2024

Transl Psychiatry

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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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Section: Discussionmentioning

confidence: 99%