Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

J Psychiatr Res. 2014 Sep;56:106-11. doi: 10.1016/j.jpsychires.2014.05.009. Epub 2014 May 29.


The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

Keywords: Adult neurogenesis; Dentate gyrus; Depression-like behavior; Fluoxetine; Stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Bromodeoxyuridine
  • Chronic Disease
  • Cyclin D2 / genetics
  • Cyclin D2 / metabolism
  • Depression / drug therapy*
  • Depression / physiopathology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Fluoxetine / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / physiopathology*
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neurogenesis / physiology*
  • Neuropsychological Tests
  • Swimming
  • Uncertainty


  • Antidepressive Agents
  • Ccnd2 protein, mouse
  • Cyclin D2
  • Fluoxetine
  • Bromodeoxyuridine