Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia
Abstract
A bidirectional relationship exists between depression and cardiovascular disease. Patients with major depression are more likely to develop cardiac events, and patients with myocardial infarction and heart failure are more likely to develop depression. A feature common to both clinical syndromes is activation of proinflammatory cytokines and stress hormones, including the hypothalamic-pituitary-adrenal axis and the renin-angiotensin-aldosterone system. In the present study we examined the hypothesis that exposure to chronic mild stress (CMS), an experimental model of depression that induces anhedonia in rats, is sufficient to activate the production of proinflammatory cytokines and stress hormones that are detrimental to the heart and vascular system. Four weeks of exposure of male, Sprague-Dawley rats to mild unpredictable environmental stressors resulted in anhedonia which was operationally defined as a reduction in sucrose intake without a concomitant effect on water intake. Humoral assays indicated increased plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), plasma renin activity, aldosterone, and corticosterone in the CMS exposed rats. Tissue TNF-alpha and IL-1beta were increased in the hypothalamus, and TNF-alpha was increased in the pituitary gland. These humoral responses to CMS, associated with anhedonia as an index of depression in the rat, are likely to be associated with neurohumoral mechanisms that may contribute to adverse cardiac events. The findings provide a basis for examining more directly the interactions among the central, endocrine, and immune systems in depression associated with heart disease.
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- Authors
- Grippo, A. J., Francis, J., Beltz, T. G., Felder, R. B., & Johnson, A. K.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Johnson, Alan Kim
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 84
- Issue
- 5
- Pages
- 697-706
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2041352084
- Semantic Scholar
- 6981ee79e05ea76b8ec3cc2987e29ff53e41a6cc
- Cited by
- 233
- References
- 65
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 12 · 2020: 5 · 2019: 10 · 2018: 15 · 2017: 14 · 2016: 20 · 2015: 18 · 2014: 18 · 2013: 16 · 2012: 16
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01hl014388-45, 5f31mh065839-02, 5r01hl057472-09)
- National Heart, Lung, and Blood Institute (HL57472, HL-14388)
- National Institute of Mental Health (MH-65839)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- chronic mild stress, anhedonia, depression, inflammatory cytokines, TNF-α, IL-1β, hypothalamic-pituitary-adrenal axis, renin-angiotensin-aldosterone system, aldosterone, corticosterone, plasma renin activity, hypothalamus, pituitary gland, cardiovascular disease, neuroendocrine-immune interaction, sucrose intake
- MeSH terms
- Aldosterone, Animals, Body Weight, Brain Chemistry, Central Nervous System, Chronic Disease, Corticosterone, Food Preferences, Hypothalamo-Hypophyseal System, Immune System, Male, Neurosecretory Systems, Renin, Renin-Angiotensin System, Stress, Psychological, Sucrose, Taste, Cytokines, Rats, Sprague-Dawley, Rats
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