Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1 beta in the rat

Rationale: The hypothesis that proinflammatory cytokines play a causative r ole in the pathophysiology of depression has been recently tested by studyi ng the effect of antidepressants on production of endogenous cytokines, and on sickness behavior induced by exogenous cytokines. In this last case, ho wever, the effect of antidepressants has been only studied on the effect of peripherally administered cytokines. Objectives: The aim of the present st udy was to determine whether the antidepressant tianeptine can attenuate bo th peripheral and central cytokine actions. Methods: Rats were injected IP with acute (10 mg/kg) or chronic (10 mg/kg. 2 times/day, 17 days) tianeptin e. The effects of this treatment were assessed on the behavioral (social ex ploration, locomotion) and metabolic (food intake, body weight) alterations induced by peripheral or central administration of the cytokine inducer li popolysaccharide (LPS) (250 mug/kg IP; 100 ng/rat ICV) or the prototypical proinflammatory cytokine interleukin-l (IL-1)beta (15 mug/rat IP; 90 ng/rat ICV). Results: Chronic, but not acute, treatment with tianeptine attenuate d the behavioral signs of sickness behavior induced by peripheral, but not central, LPS or IL-IP. Conclusions: This work, which is the first in vivo s tudy assessing the effect of an antidepressant on centrally induced immune activation, shows a clear dissociation between peripheral and central cytok ine effects, and suggests a peripheral site of action of tianeptine. It als o provides the first evidence that the protective effects of classical anti depressants on LPS-induced sickness behavior extend to an atypical antidepr essant, and that the protective effect of antidepressants also applies to I L-1 beta.