Animal Models of Depression: Molecular Perspectives
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Abstract
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.
Keywords
Animal models Antidepressants Behavioral testing Depression Resilience Stress VulnerabilityAbbreviations
- 5HT
5-Hydroxytryptamine or serotonin
- BDNF
Brain-derived neurotrophic factor
- CRF
Corticotropin-releasing factor
- CUS
Chronic unpredictable stress
- DBS
Deep brain stimulation
- DNA
Deoxyribonucleic acid
- ECT
Electroconvulsive therapy
- FST
Forced swim test
- GR
Glucocorticoid receptor
- HPA
Hypothalamic–pituitary–adrenal
- KO
Knockout
- LH
Learned helplessness
- SERT
Serotonin transporter
- TST
Tail suspension test
Notes
Acknowledgements and Financial Disclosures
Preparation of this review was supported by grants from the National Institute of Mental Health. EJN reports consulting income from Merck Research Laboratories and PsychoGenics, and a research alliance with AstraZeneca.
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