Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression
Open accessAbstract
This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05). There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.
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Preclinical studies in rodents show that IL-17A administration induces depressive-like behaviors and stress exposure elevates IL-17A levels.
“Preclinical studies in rodents corroborate these findings, showing that IL-17A administration induces depressive-like behaviors [48] and stress exposure elevates IL-17A levels [66,67,68,69].”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [68]
The Results report a significant rise in plasma IL-17 from baseline to day 120 in rats exposed to chronic mild stress. The paper calls the measured cytokine IL-17, not specifically IL-17A, so it does not establish the isoform named in the citing sentence. This citation is attached to the stress-exposure clause, not the separate claim about IL-17A administration. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIncreased levels of pro-inflammatory cytokines have been reported in brain regions of stressed animals.
“and in brain regions of stressed animals [141,142,143].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [143]
Antidepressant treatment seems to attenuate the immunological response.
“Moreover, antidepressant treatment seem to attenuate this immunological response [140,143].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [143]
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References 53 · Cited by 164
- Authors
- Lu, Y., Ho, C. S., Liu, X., Chua, A. N., Wang, W., McIntyre, R. S., & Ho, R. C.
- Affiliations
- Zhejiang University (CN)
- National University of Singapore (SG)
- Taishan Medical University (CN)
- University Health Network (CA)
- Corresponding author
- Lu, Yanxia
- Wang, Wei
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-10-19
- Volume
- 12
- Issue
- 10
- Pages
- e0186700
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5648231
- OpenAlex
- W2765484555
- Cited by
- 164
- References
- 53
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 26 · 2021: 30 · 2020: 28 · 2019: 21 · 2018: 27 · 2013: 1
- FWCI
- 6.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81600018)
- National University of Singapore (519600-X11601)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- fluoxetine, depression, chronic mild stress, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, IL-17, selective serotonin reuptake inhibitors, antidepressant effects, neuroinflammation, sucrose preference, forced swim test, rat model of depression
- MeSH terms
- Animals, Brain, Depression, Disease Models, Animal, Female, Fluoxetine, Swimming, Cytokines, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Inflammation Mediators, Rats
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