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

Biol Psychiatry. 2003 Nov 15;54(10):994-1005. doi: 10.1016/j.biopsych.2003.08.003.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Line
  • Dependovirus / metabolism
  • Depression / metabolism*
  • Depression / physiopathology
  • Disease Models, Animal
  • Embryo, Mammalian
  • Exploratory Behavior
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins
  • Humans
  • Immobilization
  • Immunohistochemistry
  • In Vitro Techniques
  • Infusion Pumps
  • Kidney
  • Luminescent Proteins / metabolism
  • Male
  • Maze Learning
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / virology
  • Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Signal Transduction / physiology
  • Swimming
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Glial Fibrillary Acidic Protein
  • Luminescent Proteins
  • Proteins
  • Green Fluorescent Proteins
  • Tyrosine 3-Monooxygenase
  • Receptor, trkB