Pharmacological validation of a chronic social stress model of depression in rats: effects of reboxetine, haloperidol and diazepam
Abstract
Chronic social stress is one of the most important factors responsible for precipitation of depressive disorder in humans. In recent years, the impact of social stress on the development of psychopathologies has been thoroughly investigated in preclinical animal studies. We have shown recently that behavioural effects of chronic social stress in rats can be reversed by citalopram and fluoxetine. This study has been designed for further pharmacological validation of the chronic social stress paradigm as a model of depressive symptoms in rats. For this, rats were subjected to 5 weeks of daily social defeat and were in parallel treatment for a clinically relevant period of 4 weeks with the antidepressant drug reboxetine (40 mg/kg/day) and the neuroleptic drug haloperidol (2 mg/kg/day). The anxiolytic diazepam (1 mg/kg) was administered acutely at the end of the stress period. Stress caused decreased locomotor and exploratory behaviours, decreased sucrose preference and increased immobility in the forced swim test, but did not affect behaviour in the elevated plus maze. Four weeks of oral treatment with reboxetine ameliorated the adverse effects of social stress and normalized behaviours related to motivation and reward sensitivity. The treatment with haloperidol worsened the adverse effects of chronic social stress having effects similar to stress on reward and motivation-related behaviours. Diazepam reduced anxiety-related behaviours as measured in elevated plus maze in control…
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Social defeat stress in mice has excellent etiological, predictive, discriminative and face validity.
“When considering experimental approaches for studying depression, social defeat stress, in particular, has been shown to have excellent etiological, predictive, discriminative and face validity.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [8]
Individual responses to social stressors within experimental preparations have become increasingly useful in modeling aspects of depression-like behavior with high construct, face, discriminative and predictive validity.
“Individual responses to social stressors within experimental preparations have thus become increasingly useful in modeling aspects of depression-like behavior with high construct, face, discriminative and predictive validity3,7–11.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [8]
Social defeat stress provides a potential means to investigate components of the basic neuropathology underlying affective illnesses, which is providing fundamentally new information about the molecular basis of affective disorders to aid in the development of novel antidepressant treatment strategies.
“Thus, social defeat stress provides a potential means to investigate components of the basic neuropathology underlying affective illnesses8,33–36, which is providing fundamentally new information about the molecular basis of affective disorders to aid in the development of novel antidepressant treatment strategies20.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [8]
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- Authors
- Rygula, R., Abumaria, N., Havemann-Reinecke, U., Rüther, E., Hiemke, C., Zernig, G., Fuchs, E., & Flügge, G.
- Affiliations
- German Primate Center (DE)
- University of Göttingen (DE)
- Johannes Gutenberg University Mainz (DE)
- Innsbruck Medical University (AT)
- Venue
- Behavioural Pharmacology
- Published
- 2008-05
- Volume
- 19
- Issue
- 3
- Pages
- 183-196
- ISSN
- 0955-8810 (ISSN-L)
- OpenAlex
- W2051886288
- Cited by
- 109
- References
- 1
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 10 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 12 · 2013: 10 · 2012: 6
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- chronic social stress, social defeat, depression model, reboxetine, haloperidol, diazepam, antidepressant efficacy, anxiolytic effects, sucrose preference, forced swim test, immobility, reward sensitivity, motivation, locomotor activity, anxiety, elevated plus maze, pharmacological validation
- MeSH terms
- Reboxetine, Animals, Antidepressive Agents, Behavior, Animal, Depression, Diazepam, Disease Models, Animal, Dose-Response Relationship, Drug, Haloperidol, Male, Morpholines, Motivation, Motor Activity, Reward, Stress, Psychological, Antipsychotic Agents, Anti-Anxiety Agents, Rats, Wistar, Rats
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