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

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 +2 more·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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  • Oxytocin acts in the brain by reducing anxiety and fear, enhancing social memory, and activating neural reward circuits.

    “Physiologically, oxytocin acts in the brain by reducing anxiety and fear [19,20], enhancing social memory [16][17][18]21] and activating neural reward circuits [21].”

    From Food sharing is linked to urinary oxytocin levels and bonding in related and unrelated wild chimpanzees (2014) · cites this paper as [19]

  • Peripheral measures of oxytocin from plasma or urine correlate positively with psychological and behavioural patterns, indicating that peripheral oxytocin levels reflect central processing of oxytocin.

    “Significantly, peripheral measures of oxytocin from plasma or urine correlate positively with psychological and behavioural patterns, such as aversion reduction in male mice [19], social contact in marmosets [40], lactation in rhesus macaques [41], rates of affiliative behaviours in pair-bonded tamarins [42] and grooming in closely bonded chimpanzees [15], indicating that peripheral oxytocin level”

    From Food sharing is linked to urinary oxytocin levels and bonding in related and unrelated wild chimpanzees (2014) · cites this paper as [19]

  • Centrally-administered oxytocin reduced anxiety-related behavior in male mice during non-social behavioral tasks.

    “Centrally-administered oxytocin reduced anxiety-related behavior in male mice during non-social behavioral tasks (Ring et al., 2006).”

    From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Ring et al., 2006

  • Prior studies have suggested that oxytocin is anxiolytic or attenuates measures of fear conditioning.

    “The results of a number of other studies have suggested that oxytocin is anxiolytic19–21 or attenuates measures of fear conditioning15–18.”

    From Oxytocin enhances observational fear in mice (2017) · cites this paper as [19]

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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
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
  • Social Sciences › Psychology › Social Psychology › 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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