Psychopharmacology

, Volume 185, Issue 2, pp 218–225

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

  • Robert H. Ring
  • Jessica E. Malberg
  • Lisa Potestio
  • Julia Ping
  • Steve Boikess
  • Bin Luo
  • Lee E. Schechter
  • Stacey Rizzo
  • Zia Rahman
  • Sharon Rosenzweig-Lipson
Original Investigation

DOI: 10.1007/s00213-005-0293-z

Cite this article as:
Ring, R.H., Malberg, J.E., Potestio, L. et al. Psychopharmacology (2006) 185: 218. doi:10.1007/s00213-005-0293-z

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 μg 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 μg, 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 μg, 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.

Keywords

OxytocinVasopressinAnxietyStressDepressionHyperthermiaAutonomicAnxiolyticBenzodiazepine

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Robert H. Ring
    • 1
  • Jessica E. Malberg
    • 1
  • Lisa Potestio
    • 1
  • Julia Ping
    • 1
  • Steve Boikess
    • 1
  • Bin Luo
    • 1
  • Lee E. Schechter
    • 1
  • Stacey Rizzo
    • 1
  • Zia Rahman
    • 1
  • Sharon Rosenzweig-Lipson
    • 1
  1. 1.Depression and Anxiety Disorders, Discovery NeuroscienceWyeth ResearchPrincetonUSA