Hypothalamic vasopressin systems are more sensitive to the long term effects of social defeat in males versus females
Open accessAbstract
Vasopressin signaling has important effects on the regulation of social behaviors and stress responses, and is considered a promising pathway to target for new therapeutics of stress-induced psychiatric disorders. Although there is evidence for sex differences in the behavioral effects of arginine vasopressin (AVP), few data have directly compared the effects of stress on endogenous AVP signaling in males and females. We used California mice (Peromyscus californicus) to study the short and long term effects of social defeat stress on AVP immunoreactive cells in the paraventricular nucleus (PVN) and the posteromedial bed nucleus of the stria terminalis (BNSTmp). Acute exposure to defeat increased AVP/c-fos cells in the PVN and SON of both males and females. In contrast, there were sex differences in the long term effects of defeat. Males but not females exposed to defeat had less avp mRNA in the PVN, and in two experiments defeat reduced the number of AVP positive cells in the caudal PVN of males but not females. Interestingly, during relatively benign social encounters with a target mouse, there was a rapid decrease in AVP percent staining (including cell bodies and fibers) in the PVN of males but not females. Defeat reduced AVP percent staining in males, but did not block the socially induced decrease in percent staining. When mice were tested in resident-intruder tests, males exposed to defeat were no less aggressive than control males whereas aggression was abolished in females. However, bouts of aggression were positively correlated with the number of AVP neurons in the BNSTmp of control males but not stressed males, suggesting that different mechanisms mediate aggression in control and stressed males. These data show that while acute AVP responses to defeat are similar in males and females, the long term effects of defeat on AVP are stronger in males.
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Prepubertal castration also increased avoidance and social vigilance toward novel naive target mice, similar to stressed adult females.
“Prepubertal castration also increased avoidance and social vigilance toward novel naive target mice, similar to stressed adult females (43, 73).”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [73]
The Introduction reports that social defeat induces greater social aversion in female California mice than in males, and Methods §2.1 identifies the mice as adults. But our copy does not report prepubertal castration or an increase in avoidance and social vigilance caused by it; searching for castration and vigilance found no such result. Page numbers were not available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSocial defeat induces a conditioned defeat phenotype in both males and females.
“Social defeat also induces a conditioned defeat phenotype in both males and females (73)”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [73]
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“In detail, VP synthesis in hypothalamic regions is similar between male and female mice (PVN and SON: Joca et al., 2013; Steinman et al., 2015), voles (PVN, SON, SCN in prairie, pine, meadow, and montane voles: Wang, 1995; Wang et al., 1996), Mongolian gerbils (PVN, medial preoptic area [MPOA],…”
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- Authors
- Steinman, M. Q., Laredo, S. A., Lopez, E. M., Manning, C. E., Hao, R. C., Doig, I. E., Campi, K. L., Flowers, A. E., Knight, J. K., & Trainor, B. C.
- Affiliations
- University of California, Davis (US)
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 51
- Pages
- 122-134
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4268083
- OpenAlex
- W2126400777
- Cited by
- 73
- References
- 19
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 9 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 9
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Research Service Award (F31 MH095253)
- NIH (R01 MH085069)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- vasopressin, social defeat stress, sex differences, hypothalamus, paraventricular nucleus, bed nucleus of the stria terminalis, c-fos, aggression, resident-intruder test, California mouse
- MeSH terms
- Animals, Arginine Vasopressin, Female, Male, Paraventricular Hypothalamic Nucleus, Peromyscus, Septal Nuclei, Sex Characteristics, Social Behavior, Social Dominance, Stress, Psychological, Supraoptic Nucleus
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