Social stress induces glucocorticoid resistance in subordinate animals
Abstract
Introducing an aggressive intruder into a cage of mice (social disruption, SDR) resulted in intense fighting and defeat of the cage residents. Defeat was accompanied by elevated levels of serum corticosterone and nerve growth factor (NGF). Repeated exposure to an intruder induced a state of glucocorticoid resistance in peripheral immune cells. The present study sought to examine the behavioral factors that mediated the development of glucocorticoid resistance following SDR. Glucocorticoid resistance developed in animals that exhibited a subordinate behavioral profile, which consisted of a low tendency for social investigation and a high level of submissive behavior in response to the intruder's attacks. Glucocorticoid resistance was also linked to the presence of injuries due to fighting, but not to changes in systemic levels of either corticosterone or NGF. Since a submissive behavioral profile is associated with increased risk for injuries due to fighting, it may be that the development of glucocorticoid resistance is an adaptive mechanism that allows the inflammatory component of wound healing to occur in the presence of high levels of corticosterone. Together, these findings demonstrate that the outcomes of social stress may be modified by physiological changes associated with wounding, as well as by behavioral variables such as social status.
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Exposure to social cues indicating an increased risk for possible physical danger induces glucocorticoid resistance.
“Evidence that even acute stress can alter glucocorticoid sensitivity is provided by research showing that exposure to social cues indicating an increased risk for possible physical danger induces glucocorticoid resistance.”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Avitsur et al., 2001
Animals injured during repeated social defeat exhibit glucocorticoid-resistant immune cells, systemic increases in glucocorticoids, exaggerated inflammatory responses, and increased pro-inflammatory gene expression in immune cells.
“Animals that sustain an injury during attack by the aggressor (Merlot et al., 2003) exhibit glucocorticoid resistant immune cells, systemic increases in glucocorticoids, exaggerated inflammatory responses (Avitsur et al., 2001; Stark et al., 2001), and increases in pro-inflammatory gene expression in immune cells (Powell et al., 2013).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Avitsur et al., 2001
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- Authors
- Avitsur, R., Stark, J. L., & Sheridan, J. F.
- Affiliations
- The Ohio State University (US)
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 39
- Issue
- 4
- Pages
- 247-257
- ISSN
- 0018-506X (ISSN-L)
- OpenAlex
- W2056550977
- Cited by
- 321
- References
- 32
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 9 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 16 · 2017: 11 · 2016: 11 · 2015: 22 · 2014: 13 · 2013: 15 · 2012: 22
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- John D. and Catherine T. MacArthur Foundation
- National Institutes of Health (1f31mh011792-01)
- National Institute of Mental Health (F31 MH11792, R01MH046801, MH46801-08)
- National Institute of Dental and Craniofacial Research (DE13749-01, P50DE013749)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Veterinary › Small Animals › Animal Behavior and Welfare Studies
- Keywords
- glucocorticoid resistance, social stress, social dominance, subordinate behavior, social disruption, corticosterone, nerve growth factor, wound healing, inflammation, social investigation, submissiveness, peripheral immune cells, mice
- MeSH terms
- Animals, Behavior, Animal, Bites and Stings, Corticosterone, Dominance-Subordination, Drug Resistance, Glucocorticoids, Hierarchy, Social, Interpersonal Relations, Male, Mice, Inbred C57BL, Stress, Psychological, Mice
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