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.
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“Another widely used rodent stress model, which distinguishes susceptible and resilient phenotypes with greater etiological validity, is repeated social defeat stress (RSDS) (21) (17).”
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- 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 ›
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