Sex Differences in Social Interaction Behavior Following Social Defeat Stress in the Monogamous California Mouse (Peromyscus californicus)
Open accessAbstract
Stressful life experiences are known to be a precipitating factor for many mental disorders. The social defeat model induces behavioral responses in rodents (e.g. reduced social interaction) that are similar to behavioral patterns associated with mood disorders. The model has contributed to the discovery of novel mechanisms regulating behavioral responses to stress, but its utility has been largely limited to males. This is disadvantageous because most mood disorders have a higher incidence in women versus men. Male and female California mice (Peromyscus californicus) aggressively defend territories, which allowed us to observe the effects of social defeat in both sexes. In two experiments, mice were exposed to three social defeat or control episodes. Mice were then behaviorally phenotyped, and indirect markers of brain activity and corticosterone responses to a novel social stimulus were assessed. Sex differences in behavioral responses to social stress were long lasting (4 wks). Social defeat reduced social interaction responses in females but not males. In females, social defeat induced an increase in the number of phosphorylated CREB positive cells in the nucleus accumbens shell after exposure to a novel social stimulus. This effect of defeat was not observed in males. The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test. These data suggest that California mice could be a useful model for studying sex differences in behavioral responses to stress, particularly in neurobiological mechanisms that are involved with the regulation of social behavior.
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In adults, sex differences in behavioral responses to defeat are independent of gonadal hormones.
“In adults, sex differences in behavioral responses to defeat are independent of gonadal hormones (42, 43), suggesting that sex differences are organized during development.”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [42]
The Discussion section, “Effects of Defeat on Corticosterone Levels” (page not available), says that ovariectomy ameliorated defeat-related changes in social interaction behavior. It concludes that ovarian hormones may mediate sex differences in responses to defeat, contrary to the claim that those differences are independent of gonadal hormones. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAdult gonadal hormones have little impact on stress-induced social avoidance.
“our previous work clearly demonstrates that adult gonadal hormones have little impact on stress-induced social avoidance (43, 50).”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [50]
The Discussion (Effects of Defeat on Corticosterone Levels; page unavailable) says that ovariectomy ameliorated defeat-induced changes in social interaction in follow-up experiments. Rather than demonstrating little impact, the paper suggests ovarian hormones are involved in the response to defeat; it identifies those follow-up findings as unpublished. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThese results contrast with adults, where social defeat decreases social approach and increases social vigilance in females but not males.
“These results contrast with observed sex differences in adults, which show that social defeat decreases social approach (38, 42, 43, 51) and increases social vigilance (40) in females but not males.”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [42]
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- Authors
- Trainor, B. C., Pride, M. C., Villalon Landeros, R., Knoblauch, N. W., Takahashi, E. Y., Silva, A. L., & Crean, K. K.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Trainor, Brian C.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-02-25
- Volume
- 6
- Issue
- 2
- Pages
- e17405
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3045459
- OpenAlex
- W1968033367
- Cited by
- 157
- References
- 80
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 16 · 2022: 10 · 2021: 14 · 2020: 5 · 2019: 9 · 2018: 17 · 2017: 15 · 2016: 7 · 2015: 10 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- University of California, Davis
- National Institute of Mental Health (R21MH090392)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- social defeat stress, sex differences, social interaction behavior, Peromyscus californicus, California mouse, mood disorders, CREB phosphorylation, nucleus accumbens shell, corticosterone, territorial aggression, stress response
- MeSH terms
- Animals, Behavior, Animal, Brain Mapping, Dominance-Subordination, Female, Male, Models, Biological, Pair Bond, Peromyscus, Sex Characteristics, Social Adjustment, Social Behavior, Stress, Psychological, Territoriality, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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