Cited by 320Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyStress Responses and Cortisol

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Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications

Ring, Robert H., Malberg, Jessica E., Potestio, Lisa, Ping, Julia, Boikess, Steve, Luo, Bin, Schechter, Lee E., Rizzo, Stacey, Rahman, Zia, Rosenzweig-Lipson, Sharon·2006·Psychopharmacology

DOI 10.1007/s00213-005-0293-z

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Abstract

Rationale Oxytocin (OT) acts as a neuromodulator/neurotransmitter within the central nervous system (CNS) and regulates a diverse range of CNS functions. Notably, evidence from studies in females has revealed an important role for OT in regulating anxiety behavior.Objectives The objective of this study was to examine the effects of OT on both behavioral and autonomic parameters of the anxiety response in male mice using three pharmacologically validated preclinical models of anxiety: the four-plate test (FPT), elevated zero maze (EZM), and stress-induced hyperthermia (SIH).Results In the FPT, both peripherally (3-30 mg/kg i.p.) and centrally (1-10 microg i.c.v.) administered OT produced dose-dependent increases in punished crossings, indicating an anxiolytic-like effect. The effects of centrally administered OT in the FPT were blocked with peripheral administration of a brain-penetrant OT receptor (OTR) antagonist WAY-162720 (30 mg/kg i.p.), and the effects of peripherally administered OT were blocked with central administration of a non-penetrant OTR antagonist L-371,257, suggesting OT acts centrally. In the EZM, centrally administered OT (0.1-1.0 microg, i.c.v.) produced significant increases in the percentage time spent in the open quadrants of the maze, comparable to alprazolam (0.5-1.0 microg, i.c.v.). In SIH, OT (1-10 mg/kg i.p.) dose-dependently attenuated stress-induced increases in core body temperature, comparable to the reference anxiolytic chlordiazepoxide (CDP) (10 mg/kg i.p.).Conclusions These results provide specific behavioral and autonomic evidence of anxiolytic-like effects for oxytocin in males and, together with previously reported observations in females, suggest the potential utility of OTR agonism as a therapeutically relevant mechanism of action for novel anxiolytics in both sexes.

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Authors: Ring, R. H., Malberg, J. E., Potestio, L., Ping, J., Boikess, S., Luo, B., Schechter, L. E., Rizzo, S., Rahman, Z., & Rosenzweig-Lipson, S.
Affiliations: Wyeth (US)
Corresponding author: Ring, Robert H.
ORCID: Ring, Robert H.
Malberg, Jessica E.
Rizzo, Stacey
Rahman, Zia
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2006-01-18
Volume: 185
Issue: 2
Pages: 218-225
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-005-0293-z
OpenAlex: W2093922373
Cited by: 319
References: 45
Citations by year: 2026: 5 · 2025: 9 · 2024: 13 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 29 · 2019: 11 · 2018: 14 · 2017: 15 · 2016: 18 · 2015: 16 · 2014: 25 · 2013: 18 · 2012: 18
FWCI: 22.49
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: oxytocin, anxiolytic-like activity, anxiety, male mice, oxytocin receptor, four-plate test, elevated zero maze, stress-induced hyperthermia, centralized management, autonomic effects, sex differences, anxiolytic drug development
MeSH terms: Animals, Behavior, Animal, Chlordiazepoxide, Dose-Response Relationship, Drug, Injections, Intraperitoneal, Injections, Intraventricular, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Oxazines, Oxytocin, Piperidines, Anti-Anxiety Agents, Receptors, Oxytocin, Benzoxazines, Mice

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Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications

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