Brain-Derived Neurotrophic Factor Conditional Knockouts Show Gender Differences in Depression-Related Behaviors

Lisa M Monteggia, Bryan Luikart, Michel Barrot, David Theobold, Irena Malkovska, Serge Nef, Luis F. Parada, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

426 Scopus citations


Background: Indirect evidence suggests that loss of brain-derived neurotrophic factor (BDNF) from forebrain regions contributes to an individual's vulnerability for depression, whereas upregulation of BDNF in these regions is suggested to mediate the therapeutic effect of antidepressants. Methods: We have tested this hypothesis by generating two independent lines of conditional BDNF knockout mice in which the BDNF gene is deleted selectively in forebrain. Results: We show that male conditional knockouts exhibit hyperactivity but normal depression-related behaviors. In contrast, female conditional knockouts display normal locomotor activity but a striking increase in depression-like behavior. We also demonstrate that loss of BDNF in both male and female mice attenuates the actions of the antidepressant desipramine in the forced swim test. Conclusions: These gender differences in depression-related behaviors in BDNF conditional knockout mice provide direct evidence for a role of BDNF in depression. The results also support the view that forebrain BDNF may be essential in mediating antidepressant efficacy.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalBiological Psychiatry
Issue number2
StatePublished - Jan 15 2007


  • BDNF
  • animal model
  • behavior
  • depression
  • gender
  • knockout

ASJC Scopus subject areas

  • Biological Psychiatry


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