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Chulalongkorn Medical Journal

Abstract

Background : An evidence suggests a potential therapeutic target of depressiontoward treating inflammation with nonsteroidal anti-inflammatory drugs(NSAIDs). However, the efficacy of the combined standard antidepressantwith NSAID treatment still remains uncertain.Objective : To examine the effects of fluoxetine (serotonin reuptake inhibitor) inadjunct with celecoxib (specific COX-2 inhibitor) on depression-likebehavior and inflammation in rats with chronic mild stress (CMS) induceddepression.Methods : The rats were divided into 4 groups: control, CMS, CMS with fluoxetinetreatment (5 mg/kg/d), and CMS with fluoxetine and celecoxib treatment(5 mg/kg/d each). All treatments were continued for 5 weeks. Thedepression-like behavior was examined using forced swimming test.Blood samples were collected for biochemical analysis of plasma levelsof cortisol, prostaglandin E2 (PGE2), interleukin-1β(IL-1β), tumor necrosisfactor-α (TNF-α, C-reactive protein (CRP), and an oxidative stressmarker malondialdehyde (MDA).Results : The combined treatment decreased depression-like behavior tothe same extent as fluoxetine treatment alone. However, the adjunctivecelecoxib significantly reversed the effect of fluoxetine in loweringthe plasma cortisol level which implied the aggravation of hypothalamicpituitary-adrenal axis (HPA axis) dysregulation, and also increased bodyweight gain compared with fluoxetine, suggesting a possibility of bodyfluid retention. Both drug treatments showed a comparable degree inlowering the plasma levels of PGE2, TNF-α, CRP and MDA. Nonetheless,fluoxetine showed no significant effect on plasma IL-1βlevel; whereasthe adjunctive celecoxib treatment lowered this proinflammatory cytokineto almost normal.Conclusion : The results suggest that the combined celecoxib treatment shows nosynergistic antidepressant effect to fluoxetine, but may exacerbatethe HPA axis hyperactivation.

Publisher

Faculty of Medicine, Chulalongkorn University

First Page

653

Last Page

665

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