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, J. Verhaagen, Eric J Nestler

Research output: Contribution to journal/periodicalArticleScientificpeer-review


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
Pages (from-to)994-1005
Number of pages12
JournalBiological Psychiatry
Issue number10
Publication statusPublished - 15 Nov 2003


  • Animals
  • Behavior, Animal
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor
  • Cell Line
  • Dependovirus
  • Depression
  • Disease Models, Animal
  • Embryo, Mammalian
  • Exploratory Behavior
  • Glial Fibrillary Acidic Protein
  • Green Fluorescent Proteins
  • Humans
  • Immobilization
  • Immunohistochemistry
  • In Vitro Techniques
  • Infusion Pumps
  • Kidney
  • Luminescent Proteins
  • Male
  • Maze Learning
  • Nucleus Accumbens
  • Proteins
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time
  • Receptor, trkB
  • Signal Transduction
  • Swimming
  • Time Factors
  • Tyrosine 3-Monooxygenase
  • Ventral Tegmental Area
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.


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