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Physiol Behav. 2015 Mar 1;140:230-5. doi: 10.1016/j.physbeh.2014.12.045. Epub 2014 Dec 30.

Fluoxetine prevents the development of depressive-like behavior in a mouse model of cancer related fatigue.

Author information

1
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH, United States.
2
Department of Physiology and Cell Biology, 370 W. 9th Ave., The Ohio State University, Columbus, OH, United States.
3
Division of Biosciences, College of Dentistry, The Ohio State University, 305 W. 12th Ave., Columbus, OH, United States.
4
College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH, United States.
5
Department of Physiology and Cell Biology, 370 W. 9th Ave., The Ohio State University, Columbus, OH, United States; College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH, United States.
6
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH, United States; Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Dr. Columbus, OH, United States.
7
College of Nursing, Marquette University Milwaukee, WI, United States. Electronic address: donnalee.mccarthy@mu.edu.

Abstract

Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue- and depressive-like behaviors. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRIs such as fluoxetine.

KEYWORDS:

Cancer; Depression; Fatigue; Fluoxetine; Neuroinflammation; Serotonin

PMID:
25554480
PMCID:
PMC4298482
DOI:
10.1016/j.physbeh.2014.12.045
[Indexed for MEDLINE]
Free PMC Article

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