Female oxytocin-deficient mice display enhanced anxiety-related behavior
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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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
- Publisher
- The Endocrine Society
- 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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