EFFECT OF SUB-ACUTE ADMINISTRATION OF CELECOXIB ON ANTIDEPRESSANT EFFECT OF FLUOXETINE IN ALBINO MICE

Abstract

Depression has recently been shown to have an inflammatory component. Celecoxib, a selective COX-2 inhibitor,  inhibits the production of prostaglandins and proinflammatory cytokines and also increases tryptophan levels and serotonin availability in depressed patients. Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are effective antidepressants, but their efficacy decreased in the presence of non-steroidal anti-inflammatory drugs (NSAIDs) in some studies. Other studies have shown that there is an  increase in antidepressant activity of fluoxetine when celecoxib is co-administered. Hence, we wanted to evaluate the effect of sub-acute administration of celecoxib on antidepressant activity of fluoxetine in albino mice. After clearance from Institutional Animal Ethics Committee, 24 healthy albino mice (20 - 30g) of either sex were divided into four groups of six mice each and administered Distilled water (control), Fluoxetine 5mg/kg (standard), Fluoxetine 5mg/kg + Ibuprofen 100mg/kg and Fluoxetine 5mg/kg + Celecoxib 5mg/kg respectively by intraperitoneal route for 21 days. Testing for antidepressant effect was done by Tail Suspension Test (TST) and Forced Swim Test (FST) in all groups at baseline (Day 0) and Day 21. Cumulative duration of immobility (which is indicative of antidepressant activity) within a 5 minute testing period was measured (in seconds) in all groups and the results were expressed as Mean ± SD. Statistical analysis was done by one-way ANOVA followed by Unpaired ‘t’ test with P<0.05 as the level of  significance (95% confidence limits). Cumulative duration of immobility (in seconds) within a 5 minute testing period was significantly decreased after drug administration in fluoxetine group in the FST and TST, compared to normal control. Duration of immobility however significantly increased in both groups  wherein ibuprofen and celecoxib were added to fluoxetine in both TST and FST. Thus, acute and sub-acute administration of celecoxib for 21 days significantly decreased the antidepressant effect of fluoxetine in albino mice.