In recent years, a potential link between inflammation and depression has been shown and the role of proinflammatory cytokines in the pathophysiology of major depressive disorders has been observed. Celecoxib (selective COX-II inhibitor) has been reported to inhibit the production of PGE-II and proinflammatory cytokines and also increase tryptophan levels and serotonin availability in depressed patients. On the other hand, duloxetine (potent SNRI) has been shown to be efficacious in inflammatory and acute pain models in rodents and synergistic interaction with NSAIDs. How-ever, the interactions of duloxetine with celecoxib are currently unknown.

We evaluated the antidepressant effect of celecoxib (15, 30 mg/kg/day for 15 days, ip) alone and in combina-tion with duloxetine (5, 10 mg/kg/day for 15 days, ip) and also the biochemical parameters in stressed mice.

Pretreatment of celecoxib (15, 30 mg/kg) for 15 days to forced swim-induced stressed mice produced significant antidepressant effect which has been evidenced by decreased in immobility time in tail suspension test (TST). Celecoxib (30 mg/kg) also showed significant increase in locomotor activity and protective effect on biochemical parameters of oxi-dative stress by reversing stress-induced increase in TBARS and reduction in GSH levels. Pretreatment with combination of celecoxib with duloxetine (5, 10 mg/kg) showed significant antidepressant and neuroprotective effects against stress in-duced depression and oxidative damage in mice at both dose levels.

This study demonstrated dose-dependent antidepressant action of celecoxib in stressed mice. The combina-tion of celecoxib with duloxetine further enhanced its antidepressant effect on TST in stressed mice. The treatment re-versed forced swim-induced elevation in TBARS levels and depleted glutathione activity, suggesting their antioxidant and protective role in brain.