Chronic Treatment with the Atypical Antidepressant Tianeptine Attenuates Sickness Behavior Induced by Peripheral but Not Central Lipopolysaccharide and Interleukin-1beta in the Rat

Rationale: The hypothesis that proinflammatory cytokines play a causative role in the pathophysiology of depression has been recently tested by studying the effect of antidepressants on production of endogenous cytokines, and on sickness behavior induced by exogenous cytokines. In this last case, however, the effect of antidepressants has been only studied on the effect of peripherally administered cytokines.

Objectives: The aim of the present study was to determine whether the antidepressant tianeptine can attenuate both 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) tianeptine. The effects of this treatment were assessed on the behavioral (social exploration, locomotion) and metabolic (food intake, body weight) alterations induced by peripheral or central administration of the cytokine inducer lipopolysaccharide (LPS) (250 microg/kg IP; 100 ng/rat ICV) or the prototypical proinflammatory cytokine interleukin-1 (IL-1)beta (15 microg/rat IP; 90 ng/rat ICV).

Results: Chronic, but not acute, treatment with tianeptine attenuated the behavioral signs of sickness behavior induced by peripheral, but not central, LPS or IL-1beta.

Conclusions: This work, which is the first in vivo study assessing the effect of an antidepressant on centrally induced immune activation, shows a clear dissociation between peripheral and central cytokine effects, and suggests a peripheral site of action of tianeptine. It also provides the first evidence that the protective effects of classical antidepressants on LPS-induced sickness behavior extend to an atypical antidepressant, and that the protective effect of antidepressants also applies to IL-1beta.