Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress

Behav Brain Res. 2009 Sep 14;202(2):245-51. doi: 10.1016/j.bbr.2009.03.040. Epub 2009 Apr 5.


Despite growing evidences of an association between brain-derived neurotrophic factor (BDNF) and antidepressant effects, the neurotrophic hypothesis of depression is challenged by the paucity of direct links between BDNF deficit and depressive-like behaviors. The unpredictable chronic mild stress (UCMS) paradigm might take our understanding a step further by examining whether a decrease in bdnf expression can lead to enhanced vulnerability to stress and prevent antidepressant efficacy in all or specific UCMS-induced alterations. Wild-type bdnf(+/+) and heterozygous bdnf(+/-) mice were exposed to an 8-week UCMS regimen and, from the third week onward, treated with either vehicle or imipramine (20mg/kg/day, ip). Physical, behavioral and biological (plasma corticosterone levels, bdnf expression in the dentate gyrus) measures were further analyzed regarding to the genotype and the treatment. Heterozygous bdnf(+/-) mice displayed hyperactivity and increase of body weight but no enhancement of the sensitivity to stress exposure in all the measures investigated here. In contrast, while imipramine treatment reduced anxiety-like behaviors in the novelty-suppressed feeding test in both genotypes, it decreased aggressiveness in the resident/intruder test and immobility in the tail suspension test in wild-type but not in heterozygous mice. Furthermore, imipramine induced a twofold increase of bdnf expression in the dentate gyrus in both genotypes, while bdnf(+/-) mice displayed roughly half-reduced level for the same treatment. In summary, we demonstrate here that depletion in BDNF dampened the antidepressant effects in several behaviors but failed to increase vulnerability to chronic stress exposure.

MeSH terms

  • Aggression / drug effects
  • Animals
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Anxiety / drug therapy
  • Body Weight / drug effects
  • Body Weight / physiology
  • Brain-Derived Neurotrophic Factor / deficiency*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Corticosterone / blood
  • Dentate Gyrus / metabolism
  • Eating / drug effects
  • Eating / physiology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Genotype
  • Imipramine / administration & dosage
  • Mice
  • Motor Activity / physiology
  • RNA, Messenger / metabolism
  • Stress, Psychological / drug therapy
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology*
  • Time Factors


  • Antidepressive Agents, Tricyclic
  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger
  • Imipramine
  • Corticosterone