Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat
Psychopharmacology. 2001-02-22; 154(1): 50-60
DOI: 10.1007/s002130000595
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1. Psychopharmacology (Berl). 2001 Feb;154(1):50-60.
Chronic treatment with the atypical antidepressant tianeptine attenuates sickness
behavior induced by peripheral but not central lipopolysaccharide and
interleukin-1beta in the rat.
Castanon N(1), Bluthé RM, Dantzer R.
Author information:
(1)INRA-INSERM U394, Neurobiologie Intégrative, Institut François Magendie,
Bordeau, France.
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.
DOI: 10.1007/s002130000595
PMID: 11292006 [Indexed for MEDLINE]