Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex

Biol Psychiatry. 2004 Apr 15;55(8):789-96. doi: 10.1016/j.biopsych.2003.12.014.


Background: Recent clinical and preclinical studies suggest that major depression may be related to impairments of structural plasticity. Consequently, antidepressants may act by restoring altered rates of cell birth or death. Here, we investigated whether the antidepressant tianeptine would affect apoptosis in an animal model of depression, the psychosocially stressed tree shrew.

Methods: Animals were subjected to a 7-day period of psychosocial stress before the onset of daily administration of tianeptine. Stress continued throughout the 28-day treatment period. In situ end labeling was used to detect apoptosis in hippocampus and adjacent temporal cortex.

Results: Both stress and tianeptine treatment had a region-specific effect. Stress increased apoptosis in the temporal cortex, while it reduced it in the Ammons Horn. No significant effect was observed in the dentate gyrus. Interestingly, tianeptine treatment significantly reduced apoptosis in the temporal cortex and dentate gyrus, both in control and stressed animals, but had no effect in the Ammons Horn. Parallel Fluoro-Jade staining indicated that this apoptosis most likely represents non-neuronal cells.

Conclusions: This is the first report showing an anti-apoptotic effect of tianeptine in hippocampal subfields and temporal cortex. These findings are consistent with current theories that ascribe enhanced general cell survival to antidepressant action.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Apoptosis / drug effects*
  • Body Weight / drug effects
  • Cell Count / methods
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects*
  • Depression / drug therapy*
  • Disease Models, Animal
  • Fluorescent Dyes / pharmacokinetics
  • In Situ Nick-End Labeling / methods
  • Male
  • Stilbamidines / pharmacokinetics
  • Stress, Psychological / drug therapy
  • Temporal Lobe / cytology
  • Temporal Lobe / drug effects*
  • Thiazepines / pharmacology*
  • Thiazepines / therapeutic use
  • Time Factors
  • Tupaiidae


  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Antidepressive Agents, Tricyclic
  • Fluorescent Dyes
  • Stilbamidines
  • Thiazepines
  • tianeptine