Depressive-like behavior induced by tumor necrosis factor-α is attenuated by m-trifluoromethyl-diphenyl diselenide in mice

A growing body of evidence associates activation of immune system with depressive symptoms. Accordingly, pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), have been shown to play a pivotal role in the pathophysiology of depression. The aim of this study was to evaluate the effectiveness of acute and subchronic treatments with (m-CF3-PhSe)2 to prevent the depressive-like behavior induced by intracerebroventricular injection of TNF-alpha in mice. TNF-alpha induced depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST) (0.1 and 0.001 fg/5 mu L/site, respectively) without changing locomotor activity, performed in the locomotor activity monitor (LAM). Acute (0.01-50 mg/kg; intragastric (i.g.); 30 min) and subchronic (0.01 and 0.1 mg/kg; i.g.; 14 days) treatments with (m-CF3-PhSe)2 at low doses were effective against the effect of TNF-alpha in the FST and TST. Nuclear factor-kappa B (NF-kappa B) and p38 mitogen-activated protein kinase (p38 MAPK), important proteins in TNF-activated signaling, were determined in the prefrontal cortex and hippocampus of mouse. TNF-alpha (0.1 5g/5 IL/site) increased NF-kappa B levels and p38 MAPK activation in both brain areas and acute (10 mg/kg; i.g.) and subchronic (0.01 mg/kg; i.g.) treatments with (m-CF3-PhSe)2 were effective in attenuating this increase. Although more studies are necessary to indicate this compound as a therapeutic alternative to depression, the antidepressant-like and anti-inflammatory effects of (m-CF3-PhSe)(2) demonstrated herein may support it as an interesting molecule in the search for new drugs to treat depressive disorders that have been largely linked to immune process and inflammation. (C) 2015 Elsevier Ltd. All rights reserved.