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PLoS One. 2017 Oct 19;12(10):e0186700. doi: 10.1371/journal.pone.0186700. eCollection 2017.

Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

Lu Y1, Ho CS2,3, Liu X4,5, Chua AN2, Wang W1, McIntyre RS6,7,8,9, Ho RC2,3.

Author information

1
Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine, Hangzhou, China.
2
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
3
Department of Psychological Medicine, National University Health System, Singapore.
4
Shandong Provincial Key Laboratory of Cerebral Microcirculation, Taishan Medical University, Tai'an, China.
5
Department of Medical Psychology, School of Basic Medical Sciences, Taishan Medical University, Tai'an, China.
6
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
7
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
8
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
9
Department of Toxicology and Pharmacology, University of Toronto, Toronto, Ontario, Canada.

Abstract

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.

PMID:
29049348
PMCID:
PMC5648231
DOI:
10.1371/journal.pone.0186700
[Indexed for MEDLINE]
Free PMC Article

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