Animal Models of Depression: Molecular Perspectives
Open accessAbstract
Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today's popular depression models creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology and automated video-tracking. This chapter reviews depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to their ease, validity and replicability, the molecular insights that they have provided, and their capacity to offer the next generation of therapeutics for depression.
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Rodent chronic stress models share repeated psychological and physiological stress over several weeks.
“Chronic stress-based models in rodents come in several varieties, but the common factor is repeated (typically daily) exposure to psychological and physiological stress beyond a period lasting for several weeks [30][31][32].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [30]
Chronic unpredictable/mild/variable stress and chronic social defeat stress are the two most commonly used animal models of depression.
“Chronic unpredictable/mild/variable stress and chronic social defeat stress are the two most commonly used animal models of depression [31, 34–38].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [31]
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- Authors
- Krishnan, V., & Nestler, E. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Krishnan, Vaishnav
- Venue
- Current Topics in Behavioral Neurosciences
- Publisher
- Springer Berlin Heidelberg
- Published
- 2011
- Volume
- 7
- Pages
- 121-147
- ISSN
- 1866-3370 (ISSN-L)
- 1866-3389
- PMC
- PMC3270071
- OpenAlex
- W84932982
- Cited by
- 528
- References
- 131
- Citations by year
- 2026: 13 · 2025: 35 · 2024: 40 · 2023: 38 · 2022: 49 · 2021: 57 · 2020: 42 · 2019: 45 · 2018: 39 · 2017: 42 · 2016: 37 · 2015: 33 · 2014: 27 · 2013: 14 · 2012: 9
- FWCI
- 71.79
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current topics in behavioral neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH051399, P50MH066172)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- animal models of depression, major depressive disorder, forced swim test, social defeat stress, chronic stress, secondary depression, antidepressant mechanism, behavioral assays, video tracking
- MeSH terms
- Animals, Antidepressive Agents, Depression, Major Depressive Disorder, Disease Models, Animal, Humans, Stress, Psychological
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