Chulalongkorn Medical Journal


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.



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