Fluoxetine attenuates stress-induced depression-like behavior due to decrease in pro-inflammatory cytokines in male rats

Author:

Nabirumbi Ritah12,Onohuean Hope13ORCID,Drago Kato Charles45,Alagbonsi Abdullateef Isiaka6,Adedeji Ahmed A.17

Affiliation:

1. Biopharmaceutics Unit, Department of Pharmacology & Toxicology, School of Pharmacy, Kampala International University, Ishaka-Bushenyi, Uganda

2. Department of Pharmacology, Kabale University, Kabale, Uganda

3. Biomolecules, Metagenomics, Endocrine and Tropical Disease Research Group (BMETDREG), Kampala International University, Ishaka-Bushenyi, Uganda

4. College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda

5. Department of Microbiology & Immunology, Kampala International University, Bushenyi, Uganda

6. Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Republic of Rwanda

7. Department of Pharmacology, Faculty of Basic Medical Science, OOACHS, Olabisi Onabanjo University, Sagamu Ogun State, Nigeria

Abstract

Background: Pro-inflammatory cytokines are implicated in depression caused by both environmental- and alcohol-induced stress. The purpose of the study was to investigate the cytokine levels in serum and hippocampus following induction of depression-like behaviors (DLB) by either forced swimming test (FST) or ethanol-induced DLB (EID). We also investigated the effect of prior administration of antidepressant drug fluoxetine on cytokines in animals exposed to both models of DLB. Methods: Animals were pretreated with fluoxetine before inducing DLB, while DLB was induced in some animals using FST and ethanol in different groups of rats without fluoxetine pretreatment. The ELISA was used to detect changes in cytokine (IL-1β, IL-6, and TNF-α) levels in serum and hippocampus. Results: The mean levels of IL-1β and IL-6 measured in serum and hippocampus were significantly higher in FST and EID models when compared to the control group. The serum concentrations of IL-1β and IL-6 were significantly reduced in animals pre-treated with 5 mg/kg and 10 mg/kg of fluoxetine in both FST and EID models when compared to the untreated FST and EID groups respectively. Conclusions: In conclusion, both environment and alcohol can induce stress and DLB in rats with similar intensity, and their mechanisms of DLB induction involve activation of pro-inflammatory cytokines. Moreover, fluoxetine can prevent stress-induced inflammation in models of DLB.

Funder

Medical Education Programme Initiative of Medical Education Support for Ugandan

Publisher

SAGE Publications

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