Cited by 201Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

Female oxytocin-deficient mice display enhanced anxiety-related behavior

Mantella, Rose C., Vollmer, Regis R., Li, Xia, Amico, Janet A.·2003·Endocrinology

Abstract

Previous studies have suggested that oxytocin (OT) may be anxiolytic in female laboratory rats and mice. The elevated plus-maze was used to compare anxiety-related behaviors of OT-deficient (OT-/-) and wild-type (OT+/+) mice. Female OT-/- mice displayed increased anxiety-related behavior compared with OT+/+ mice. The percentage of entries (P < 0.0002) and time spent (P < 0.003) in the open arms was less in female OT-/- than OT+/+ mice. Administration of synthetic OT, 2 ng by intracerebroventricular (icv) injection to female OT-/- mice, increased the percentage of entries (P < 0.003) and time spent (P < 0.004) in the open arms compared with artificial cerebrospinal fluid female OT-/- mice. Administration of an OT receptor antagonist (Atosiban, d[Dtyr(Et)(2), Thr(4)]ornithine vasotocin) 100 ng icv, to female OT+/+ mice increased anxiety-related behavior by decreasing the percentage of entries (P < 0.01) and time spent (P < 0.04) in the open arms compared with artificial cerebrospinal fluid-treated controls. Central infusion of an OT receptor antagonist, 100 ng icv, before administration of synthetic OT, 2 ng icv, in female OT-/- mice blocked the anxiolytic affect of OT. In contrast, male OT-/- mice displayed decreased anxiety-related behavior compared with male OT+/+ mice. The percentage of entries (P < 0.007) and time spent (P < 0.004) in the open arms was greater in male OT-/- vs. OT+/+ mice. Our findings indicate that OT pathways play a role in modulating anxiety in female mice of the C57BL/6 background, and the effect is mediated by the OT receptor.

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Crossref · 10.1210/en.2002-0197

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  • Female mice lacking the oxytocin gene exhibit enhanced corticosteroid responses to psychogenic stressors and enhanced anxiety on the elevated plus-maze compared to wildtype controls.

    “Similarly, female mice lacking the oxytocin gene exhibit enhanced corticosteroid responses to psychogenic stressors and enhanced anxiety on the elevated plus-maze compared to wildtype controls (Amico et al., 2004; Mantella et al., 2003).”

    From Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome (2012) · cites this paper as Mantella et al., 2003

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Authors
Mantella, R. C., Vollmer, R. R., Li, X., & Amico, J. A.
Affiliations
University of Pittsburgh (US)
Corresponding author
Mantella, Rose C.
ORCID
Li, Xia
Venue
Endocrinology
Published
2003-06
Volume
144
Issue
6
Pages
2291-2296
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2077621719
Cited by
200
References
26
Citations by year
2026: 3 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 21 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 10
FWCI
14.44
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hd037268-04)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD37268)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
oxytocin, oxytocin receptor, anxiety, sex differences, anxiolytic effects, atosiban, intracerebroventricular administration, elevated plus maze, C57BL/6 mice
MeSH terms
Animals, Anxiety, Behavior, Animal, Female, Hormone Antagonists, Injections, Intraventricular, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Oxytocin, Vasotocin, Receptors, Oxytocin, Maze Learning, Mice

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