Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice

Life Sci. 2012 Dec 17;91(25-26):1252-62. doi: 10.1016/j.lfs.2012.09.023. Epub 2012 Oct 13.


Aims: Tianeptine is an atypical antidepressant drug that has a different mechanism of action than other antidepressants. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia. The present study was undertaken to investigate effects of chronic administration of tianeptine or olanzapine on unpredictable chronic mild stress (UCMS)-induced depression-like behavior in mice compared to a widely used SSRI antidepressant, fluoxetine.

Main methods: Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7weeks and were treated intraperitoneally with tianeptine (5mg/kg), olanzapine (2.5mg/kg), fluoxetine (15mg/kg) or vehicle for 5weeks (n=7-8 per group).

Key findings: All the drugs tested prevented stress-induced deficit in coat state during UCMS procedure, in grooming behavior in the splash test, decreased the attack frequency in the resident intruder test and decreased the immobility time in the tail suspension test. In the open field test olanzapine had anxiolytic-like effects in both stressed and non-stressed mice. Tianeptine, olanzapine and fluoxetine decreased the enhanced levels of plasma ACTH and IL-6. Chronic treatment with tianeptine resulted in a significant increase in both total number and density of BrdU-labeled cells in stressed animals, while fluoxetine and olanzapine had a partial effect.

Significance: The results of this study support the hypothesis that tianeptine can be as effective as fluoxetine for the treatment of depression in spite of the differences in the mechanism of action of these drugs. Moreover, olanzapine could be used effectively in psychotic patients with depression.

Publication types

  • Comparative Study

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Benzodiazepines / pharmacology*
  • Depression / drug therapy*
  • Disease Models, Animal
  • Fluoxetine / pharmacology*
  • Injections, Intraperitoneal
  • Interleukin-6 / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Olanzapine
  • Stress, Psychological / drug therapy
  • Thiazepines / pharmacology*


  • Antidepressive Agents
  • Interleukin-6
  • Thiazepines
  • Fluoxetine
  • tianeptine
  • Benzodiazepines
  • Adrenocorticotropic Hormone
  • Olanzapine