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Cited by 42Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolTreatment of Major Depression

Stress-induced alterations of mesocortical and mesolimbic dopaminergic pathways

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Quessy, F., Bittar, T., Blanchette, L. J., Lévesque, M., Labonté, B.·2021·Scientific Reports
DOI 10.1038/s41598-021-90521-yPMC PMC8154906
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Abstract

Our ability to develop the cognitive strategies required to deal with daily-life stress is regulated by region-specific neuronal networks. Experimental evidence suggests that prolonged stress in mice induces depressive-like behaviors via morphological, functional and molecular changes affecting the mesolimbic and mesocortical dopaminergic pathways. Yet, the molecular interactions underlying these changes are still poorly understood, and whether they affect males and females similarly is unknown. Here, we used chronic social defeat stress (CSDS) to induce depressive-like behaviors in male and female mice. Density of the mesolimbic and mesocortical projections was assessed via immuno-histochemistry combined with Sholl analysis along with the staining of activity-dependent markers pERK and c-fos in the ventral tegmental area (VTA), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Our results show that social stress decreases the density of TH+ dopaminergic axonal projections in the deep layers of the mPFC in susceptible but not resilient male and female mice. Consistently, our analyses suggest that pERK expression is decreased in the mPFC but increased in the NAc following CSDS in males and females, with no change in c-fos expression in both sexes. Overall, our findings indicate that social defeat stress impacts the mesolimbic and mesocortical pathways by altering the molecular interactions regulating somatic and axonal plasticity in males and females.

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  • Chronic stress disrupts key neurotransmitter systems, alters neuronal connectivity, and disturbs synaptic network activity, leading to dysregulated excitatory glutamatergic signaling, impaired dopaminergic transmission, and altered inhibitory GABAergic signaling in specific brain regions.

    “Concurrently, chronic stress disrupts key neurotransmitter systems, alters neuronal connectivity, and disturbs synaptic network activity, leading to, for example, dysregulated excitatory glutamatergic signaling, impaired dopaminergic transmission, and altered inhibitory GABAergic signaling in specific brain regions [4,24,29,35,36,37].”

    From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [36]

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Authors
Quessy, F., Bittar, T., Blanchette, L. J., Lévesque, M., & Labonté, B.
Affiliations
Université Laval (CA)
Corresponding author
  • Lévesque, M.
  • Labonté, B.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-05-26
Volume
11
Issue
1
Pages
11000-11000
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-90521-y
PMC
PMC8154906
OpenAlex
W3165499257
Cited by
42
References
17
Citations by year
2026: 6 · 2025: 15 · 2024: 13 · 2023: 3 · 2022: 3 · 2021: 2
FWCI
2.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fonds de Recherche du Québec-Santé
  • Natural Sciences and Engineering Research Council of Canada
  • National Alliance for Research on Schizophrenia and Depression
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
chronic social defeat stress, depression-like behavior, ventral tegmental area, nucleus accumbens, medial prefrontal cortex, ERK1/2 phosphorylation, c-fos, sex differences, stress resilience, axonal plasticity
MeSH terms
Social Defeat, Animals, Depression, Dopamine, Female, Male, Mice, Inbred C57BL, Neural Pathways, Nucleus Accumbens, Stress, Psychological, Proto-Oncogene Proteins c-fos, Prefrontal Cortex, Ventral Tegmental Area, Mice, Dopaminergic Neurons

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