Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: A role in depression

Amelia J. Eisch, Carlos A. Bolaños, Joris De Wit, Ryan D. Simonak, Cindy M. Pudiak, Michel Barrot, Joost Verhaagen, Eric J. Nestler

Research output: Contribution to journalArticle

323 Scopus citations

Abstract

Background: Previous work has shown that brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), are involved in appetitive behavior. Here we show that BDNF in the ventral tegmental area-nucleus accumbens (VTA-NAc) pathway is also involved in the development of a depression-like phenotype. Methods: Brain-derived neurotrophic factor signaling in the VTA-NAc pathway was altered in two complementary ways. One group of rats received intra-VTA infusion of vehicle or BDNF for 1 week. A second group of rats received intra-NAc injections of vehicle or adeno-associated viral vectors encoding full-length (TrkB.FL) or truncated (TrkB.T1) TrkB; the latter is kinase deficient and serves as a dominant-negative receptor. Rats were examined in the forced swim test and other behavioral tests. Results: Intra-VTA infusions of BDNF resulted in 57% shorter latency to immobility relative to control animals, a depression-like effect. Intra-NAc injections of TrkB.T1 resulted in and almost fivefold longer latency to immobility relative to TrkB.FL and control animals, an antidepressant-like effect. No effect on anxiety-like behaviors or locomotion was seen. Conclusions: These data suggest that BDNF action in the VTA-NAc pathway might be related to development of a depression-like phenotype. This interpretation is intriguing in that it suggests a role for BDNF in the VTA-NAc that is opposite of the proposed role for BDNF in the hippocampus.

Original languageEnglish (US)
Pages (from-to)994-1005
Number of pages12
JournalBiological Psychiatry
Volume54
Issue number10
DOIs
StatePublished - Nov 15 2003

Keywords

  • Adeno-associated virus
  • Brain-derived neurotrophic factor
  • Forced swim test
  • Nucleus accumbens
  • Tyrosine kinase receptor B
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biological Psychiatry

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    Eisch, A. J., Bolaños, C. A., De Wit, J., Simonak, R. D., Pudiak, C. M., Barrot, M., Verhaagen, J., & Nestler, E. J. (2003). Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: A role in depression. Biological Psychiatry, 54(10), 994-1005. https://doi.org/10.1016/j.biopsych.2003.08.003