The anti-inflammatory drugs ibuprofen, celecoxib, and etanercept prevented cyclosporine A form initiating depression-like behavior in mice

Abstract

Cyclosporine A (CYA), is used to prevent graft rejection, but it may cause depression in individuals. Anti-inflammatory drugs are associated with antidepressant effects, the aim was evaluating the effect of nonsteroidal anti-inflammatory drugs (NSAID) (ibuprofen, celecoxib), and tumor necrosis factor-α blocker (etanercept) pretreatment on depressive behavior induced by CYA (20 mg/kg) in male mice (25±2 g). The pretreatment with ibuprofen (50 mg/kg), or celecoxib (25 mg/kg) were applied intraperitoneal for 3 days. Etanercept (1 mg/kg) subcutaneously was injected on days 1 and 3. After the locomotor test, immobility during the forced swimming test (FST), and sucrose preference (SP) were evaluated. Pretreatment with each of the drugs ibuprofen, celecoxib, and etanercept reversed the increased immobility time during FST induced by CYA after the first dose (149±7.07 s vs. control 100±10.4 s, p<0.01) and the last dose (179±6.4 s vs. control group 101±16 s, p<0.01). The SP increased following pretreatment with the selected drugs. While, the treatments did not cause significant changes in the locomotor test. The NSAIDs, and etanercept reversed CYA despair behavior during FST and anhedonia in SP test. Therefore the co-administrating of these drugs with CYA may be useful in preventing CYA psychological side effects that warrants precise evaluations.

Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In all preclinical studies (17/17, 100%), regardless of the depression model, antidepressant effect of celecoxib was reported. Most included reports have pointed to the antidepressant effect of celecoxib in monotherapy [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87]. Interestingly, two studies indicated that celecoxib might enhance the antidepressant effects of fluoxetine and bupropion [75,88].…”

“…Interestingly, two studies indicated that celecoxib might enhance the antidepressant effects of fluoxetine and bupropion [75,88]. In nine studies, celecoxib alone or with co-administration of antidepressants improved behavioral despair in forced swimming test (FST) [74][75][76][80][81][82][84][85][86] and in four studies in tail suspension test (TST) [75,76,78,83]. In eight studies, a positive effect on anhedonia as measured by the sucrose preference test (SPT) was found [73,76,77,81,82,[84][85][86].…”

“…In nine studies, celecoxib alone or with co-administration of antidepressants improved behavioral despair in forced swimming test (FST) [74][75][76][80][81][82][84][85][86] and in four studies in tail suspension test (TST) [75,76,78,83]. In eight studies, a positive effect on anhedonia as measured by the sucrose preference test (SPT) was found [73,76,77,81,82,[84][85][86]. Four studies showed reduced anxiety and increased locomotor activity in open field test (OFT) [72][73][74]87] and one in evaluated plus maze (EPM) [76].…”

“…The models used to assess the influence of celecoxib on anxiety or depressive symptoms were as follows: stress-induced depressive-like behavior [73,77,78,81,84,86,88], induced by inflammation [74,79,82,85], diet-induced [76], different disease models [75,80,83], and bulbectomy [72,87].…”