The Effects of Fluoxetine Treatment in a Chronic Mild Stress Rat Model on Depression-Related Behavior, Brain Neurotrophins and ERK Expression

  • Maya First
  • Irit Gil-Ad
  • Michal TalerEmail author
  • Igor Tarasenko
  • Nurit Novak
  • Abraham Weizman


Depression is associated with hippocampus (HC) volume loss. Chronic mild stress (CMS) in rats is a model of depression. Antidepressants attenuate HC volume loss and reverse the depression-like symptoms of stressed animals. We evaluated the effect of CMS and the selective serotonin reuptake inhibitor, fluoxetine (FLX) treatment on behavioral and cognitive parameters in rats, and on HC and frontal cortex (FC) neurotrophic factors levels. Male rats were exposed sequentially, over a period of 5 weeks, to a variety of mild stressors. FLX (5 mg/kg/day ip) was administered to the stressed group and controls (unstressed). After 5 weeks of CMS, animals were tested using the Morris Water Maze (MWM). In the MWM, we observed that FLX had a transitory effect on unstressed rats. CMS reduced insulin-like growth factor-1 receptor (IGF-1R) levels in the HC whereas after FLX treatment these levels reverted to normal range. CMS rats revealed a significant decrease in extracellular signal-regulated kinase (ERK) phosphorylation in both HC and FC regions, while FLX normalized these levels. This study suggests that IGF-1R and ERK may have a role in mediating the neural stress response and the mode of action of FLX. This role seems to be independent of the BDNF alterations.


Chronic mild stress (CMS) Insulin-like growth factor-1 receptor (IGF-1R) Extracellular signal-regulated kinase (ERK) Hippocampus Frontal cortex 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Maya First
    • 1
  • Irit Gil-Ad
    • 1
  • Michal Taler
    • 1
    Email author
  • Igor Tarasenko
    • 1
  • Nurit Novak
    • 1
  • Abraham Weizman
    • 1
    • 2
  1. 1.Laboratory of Biological Psychiatry, Felsenstein Medical Research Center and Sackler Faculty of MedicineTel-Aviv UniversityPetah TikvaIsrael
  2. 2.Research Unit, Geha Mental Health CenterPetah TikvaIsrael

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