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Cited by 420Stress Responses and CortisolTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

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Neurobiology of chronic mild stress: Parallels to major depression

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Hill, Matthew N., Hellemans, Kim G.C., Verma, Pamela, Gorzalka, Boris B., Weinberg, Joanne·2012·Neuroscience & Biobehavioral Reviews
DOI 10.1016/j.neubiorev.2012.07.001PMC PMC4821201
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Abstract

The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression.

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  • Stressful events in childhood, adolescence, or adulthood can trigger psychiatric disorders such as depression.

    “Stressful events in childhood, adolescence, or adulthood are considered villains due to their ability to trigger psychiatric disorders, such as depression or depressive-like behaviors in animals [3],[4].”

    From Stress and serum cortisol levels in major depressive disorder: a cross-sectional study (2020) · cites this paper as [32]

    The Introduction (page unavailable) describes life stressors as a precipitating factor for depressive episodes in humans and chronic mild stress as a rodent model of depression. It does not establish the claim for stressful events at each specified life stage—childhood, adolescence, and adulthood—and cautions that stress does not invariably lead to depression. (LLM, conf=0.85)

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Metadata

Authors
Hill, M. N., Hellemans, K. G. C., Verma, P., Gorzalka, B. B., & Weinberg, J.
Affiliations
  • University of Calgary (CA)
  • Carleton University (CA)
  • University of British Columbia (CA)
Corresponding author
Hill, Matthew N.
ORCID
Venue
Neuroscience & Biobehavioral Reviews
Publisher
Elsevier BV
Published
2012-10
Volume
36
Issue
9
Pages
2085-2117
ISSN
0149-7634 (ISSN-L)
DOI
10.1016/j.neubiorev.2012.07.001
PMC
PMC4821201
OpenAlex
W2045595011
Cited by
420
References
28
Citations by year
2026: 16 · 2025: 17 · 2024: 31 · 2023: 30 · 2022: 27 · 2021: 33 · 2020: 35 · 2019: 26 · 2018: 28 · 2017: 29 · 2016: 39 · 2015: 44 · 2014: 39 · 2013: 21 · 2012: 5
FWCI
2.29
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience & Biobehavioral Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Canadian Institutes of Health Research
  • National Institute on Alcohol Abuse and Alcoholism (R37AA007789)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
chronic mild stress, animal models of depression, major depressive disorder, anhedonia, reward salience, neurochemistry, neurotrophins, cellular plasticity, translational validity
MeSH terms
Animals, Brain, Major Depressive Disorder, Depressive Disorder, Major, Disease Models, Animal, Synaptic Transmission, Stress, Psychological

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