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 language | English |
|---|---|
| Pages (from-to) | 994-1005 |
| Number of pages | 12 |
| Journal | Biological Psychiatry |
| Volume | 54 |
| Issue number | 10 |
| Publication status | Published - 15 Nov 2003 |
Keywords
- 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.