Possible Modulating Effects of Celecoxib (COX II Inhibitor) on Antide-pressant Action of Duloxetine (SNRI) in Stressed Mice

Razia Khanam
2012 Open Conference Proceedings Journal  
Rationale: 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
more » ... be efficacious in inflammatory and acute pain models in rodents and synergistic interaction with NSAIDs. However, the interactions of duloxetine with celecoxib are currently unknown. Objective: We evaluated the antidepressant effect of celecoxib (15, 30 mg/kg/day for 15 days, ip) alone and in combination with duloxetine (5, 10 mg/kg/day for 15 days, ip) and also the biochemical parameters in stressed mice. Results: 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 oxidative 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 induced depression and oxidative damage in mice at both dose levels. Conclusions: This study demonstrated dose-dependent antidepressant action of celecoxib in stressed mice. The combination of celecoxib with duloxetine further enhanced its antidepressant effect on TST in stressed mice. The treatment reversed forced swim-induced elevation in TBARS levels and depleted glutathione activity, suggesting their antioxidant and protective role in brain. © Khanam et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
doi:10.2174/2210289201203010035 fatcat:rvtg2a4zbvdhjauaswwpmea3ky