The NSAIDs Ibuprofen and Celecoxib and the TNF-α Blocker Etanercept Prevented Cyclosporine A-Induced 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. © 2021, Hacettepe University, Faculty of Pharmacy. All rights reserved.