The DOI matches its Crossref record; 227 of the 229 references it cites were found in a registry or an index.
Defeat stress in rodents: From behavior to molecules
Abstract
Mood and anxiety disorders are prevalent conditions affecting one out of four people during lifetime. The development of high validity animal models to study these disorders has been a major challenge in the past. When considering experimental approaches for studying affective disorders, the social defeat paradigm has been shown to have etiological, predictive and face validity. Here, we explain the general principle of social defeat stress paradigms, with a strong focus on the resident-intruder model and compare different experimental settings as published to date. We discuss behavioral changes described in defeated animals as well as changes in the animal's physiological parameters. In addition, we provide an overview of the molecular adaptations that are found in animals subjected to defeat stress, with special attention to neural circuits and neuroendocrine signaling. Defeat produces specific behaviors resembling the signs and symptoms of humans with affective disorders, such as anhedonia, social avoidance, despair and anxiety. These can be linked to a wide range of physiological changes-ranging from cardiovascular changes to alterations in the immune system- or by disturbances in specific neurotransmitter systems, in particular serotonin and dopamine. The defeat stress model thus impacts on several functional domains of behavior and may mimic cardinal features of a multitude of psychiatric disorders including depression, post-traumatic stress disorder and schizophrenia. This manuscript critically reviews the core findings, strengths and limitations of the range of animal studies in this field and provides future perspectives.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Citations
Cites
Items 201–227 of 227
Kieran, N., Ou, X., & Iyo, A. H. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.12.032 · Cited by 43
Kinn, A. M., Grønli, J., Fiske, E., Kuipers, S. D., Ursin, R., Murison, R. C. C., & Portas, C. M. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.07.031 · Cited by 39
Effects of chronic social defeat on expression of dopamine β‐hydroxylase in rat brains
Fan, Y., Chen, P., Li, Y., & Zhu, M. (2013) · Synapse · doi:10.1002/syn.21641 · Cited by 36
Palanza, P., Parmigiani, S., & Saal, F. S. V. (1994) · Animal Behaviour · doi:10.1006/anbe.1994.1235 · Cited by 35
Adamcio, B., Havemann‐Reinecke, U., & Ehrenreich, H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.05.030 · Cited by 34
Is full physical contact necessary for buffering effects of pair housing on social stress in rats?
Nakayasu, T., & Kato, K. (2010) · Behavioural Processes · doi:10.1016/j.beproc.2010.12.002 · Cited by 34
Ethopharmacology of copulatory disorder induced by chronic social conflict in male mice
Yoshimura, H., & Kimura, N. (1991) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80138-1 · Cited by 34
Erhardt, A., Müller, M., Rödel, A., Welt, T., Ohl, F., Holsboer, F., & Keck, M. E. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108089813 · Cited by 34
Principles for developing animal models of military PTSD
Daskalakis, N. P., & Yehuda, R. (2014) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v5.23825 · Cited by 32
Lee, M. R., Cacic, K., Demers, C. H., Haroon, M., Heishman, S. J., Hommer, D. W., Epstein, D. H., Ross, T. J., Stein, E. A., Heilig, M. A., et al. (2013) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2013.11.022 · Cited by 32
Social stress decreases marking behavior independently of testosterone in Mongolian gerbils
Yamaguchi, H., Kikusui, T., Takeuchi, Y., Yoshimura, H., & Mori, Y. (2005) · Hormones and Behavior · doi:10.1016/j.yhbeh.2004.12.009 · Cited by 30
Social features of scent-donor mice modulate scent marking of C57BL/6J recipient males
Arakawa, H., Arakawa, K., Blanchard, D. C., & Blanchard, R. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.07.007 · Cited by 29
Brain Norepinephrine System as a Target for Antidepressant and Mood Stabilizing Medications
Dremencov, E., Mansari, M. E., & Blier, P. (2009) · Current Drug Targets · doi:10.2174/138945009789735165 · Cited by 29
Social subordination and scent-marking in male mongolian gerbils (Meriones unguiculatus)
Yahr, P. (1977) · Animal Behaviour · doi:10.1016/0003-3472(77)90005-7 · Cited by 26
Kemppainen, H., Raivio, N., Nurmi, H. J., & Kiianmaa, K. (2010) · Alcohol and Alcoholism · doi:10.1093/alcalc/agp086 · Cited by 25
Shimozuru, M., Kikusui, T., Takeuchi, Y., & Mori, Y. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.05.018 · Cited by 24
Regulation of NGF, BDNF and LNGFR gene expression in ROS 17/2.8 cells
Jehan, F. (1996) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(95)03710-1 · Cited by 23
Social defeat differentially affects immune responses in Siberian hamsters (Phodopus sungorus)
Chester, E. M., Bonu, T., & Demas, G. E. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.04.016 · Cited by 22
Mechanisms of Glucocorticoid Hormone Action
Slater, E. P., Anderson, T., Cattini, P. A., ISAACS, R. E., Birnbaum, M. J., Gardner, D. G., Eberhardt, N. L., & Baxter, J. D. (1986) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5101-6_5 · Cited by 22
Social confrontation in male guinea pigs: Behavior, experience, and complement activity
Stefanski, V., & Hendrichs, H. (1996) · Physiology & Behavior · doi:10.1016/0031-9384(95)02269-4 · Cited by 21
Razzoli, M., Andreoli, M., Maraia, G., Di Francesco, C., & Arban, R. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.07.022 · Cited by 20
Changes in Various Measures of Immune Status in Mice Subject to Chronic Social Conflict
Gryazeva, N. I., Shurlygina, A. V., Verbitskaya, L. V., Mel'nikova, E. V., Kudryavtseva, N. N., & Труфакин, В. А. (2001) · Neuroscience and Behavioral Physiology · doi:10.1023/a:1026634532698 · Cited by 19
Opposing effects of positive and negative stress on hippocampal plasticity over the lifespan
Wosiski‐Kuhn, M., & Stranahan, A. M. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.003 · Cited by 18
Role of anxiety in subordinate male mice sexual behavior
D'Amato, F. R., & Pavone, F. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90655-y · Cited by 16
Huang, C.-H., Kuo, M.-T., & Lai, W. (2010) · Behavioural Processes · doi:10.1016/j.beproc.2010.10.005 · Cited by 14
Reijmers, L. G. J. E., Hoekstra, K., Burbach, J. P. H., van Ree, J. M., & Spruijt, B. M. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01834-1 · Cited by 10
Willey, A. R., & SPEAR, L. P. (2013) · Developmental Psychobiology · doi:10.1002/dev.21143 · Cited by 6
Flagged first, then by citations
2 of the 229 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- Bailey, 2007, Repeated social defeat increases the bactericidal activity of splenic macrophages through a Toll-like receptor-dependent pathway, Am. J. Physiol. Regul. Integr. Comp. Physiol., 293, R1180, 10.1152/ajpregu.00307.2007 · DOI · Paper page
- Foster, 2006, Social defeat increases food intake, body mass, and adiposity in Syrian hamsters, Am. J. Physiol. Regul. Integr. Comp. Physiol., 290, R1284, 10.1152/ajpregu.00437.2005 · DOI
- Kinn, 2008, A double exposure to social defeat induces sub-chronic effects on sleep and open field behaviour in rats, Physiol. Behav., 95, 553, 10.1016/j.physbeh.2008.07.031 · DOI
- Kudryavtseva, 1991, Social model of depression in mice of C57BL/6J strain, Pharmacol. Biochem. Behav., 38, 315, 10.1016/0091-3057(91)90284-9 · DOI · Paper page
- Watt, 2009, Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults, Behav. Neurosci., 123, 564, 10.1037/a0015752 · DOI
Cited by
Sorted by citations
Animal models of major depression: drawbacks and challenges
Planchez, B., Surget, A., & Belzung, C. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-02084-y · Cited by 480
Neurobiology of Resilience: Interface Between Mind and Body
Cathomas, F., Murrough, J. W., Nestler, E. J., Han, M.-H., & Russo, S. J. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.04.011 · Cited by 296
“Another widely used rodent stress model, which distinguishes susceptible and resilient phenotypes with greater etiological validity, is repeated social defeat stress (RSDS) (21) (17).”
BackgroundDeslauriers, J., Tóth, M., Der‐Avakian, A., & Risbrough, V. B. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.019 · Cited by 272
Rodent models of post-traumatic stress disorder: behavioral assessment
Verbitsky, A., Dopfel, D., & Zhang, N. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0806-x · Cited by 260
Migration and psychosis: a meta-analysis of incidence studies
Selten, J., van der Ven, E., & Termorshuizen, F. (2019) · Psychological Medicine · doi:10.1017/s0033291719000035 · Cited by 210
Metadata
- Authors
- Hammels, C., Pishva, E., De Vry, J., van den Hove, D. L. A., Prickaerts, J., van Winkel, R., Selten, J.-P., Lesch, K.-P., Daskalakis, N. P., Steinbusch, H. W. M., van Os, J., Kenis, G., & Rutten, B. P. F.
- Affiliations
- Maastricht University (NL)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Rutten, Bart P.F.
- ORCID
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 59
- Pages
- 111-140
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2175484872
- Cited by
- 230
- References
- 229
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 18 · 2023: 12 · 2022: 18 · 2021: 28 · 2020: 50 · 2019: 28 · 2018: 14 · 2017: 17 · 2016: 20
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Lirias (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- Netherlands Organisation for Scientific Research (916.11.086)
- European Community's Seventh Framework Program
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- social defeat stress, depression, post-traumatic stress disorder, schizophrenia, anhedonia, social avoidance, neuroendocrine signaling, serotonin, dopamine, immune system alterations, cardiovascular changes, neural circuits, face validity
- MeSH terms
- Animals, Anxiety Disorders, Behavior, Animal, Depression, Disease Models, Animal, Humans, Social Behavior, Stress, Psychological
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 ›
Are you an author, or do you see a problem with this page? Request a review
