PMID- 14625141
OWN - NLM
STAT- MEDLINE
DCOM- 20031229
LR  - 20220318
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 54
IP  - 10
DP  - 2003 Nov 15
TI  - Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens 
      pathway: a role in depression.
PG  - 994-1005
AB  - 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.
FAU - Eisch, Amelia J
AU  - Eisch AJ
AD  - Department of Psychiatry, The University of Texas Southwestern Medical Center, 
      Texas, Dallas 75390-9070, USA.
FAU - Bolanos, Carlos A
AU  - Bolanos CA
FAU - de Wit, Joris
AU  - de Wit J
FAU - Simonak, Ryan D
AU  - Simonak RD
FAU - Pudiak, Cindy M
AU  - Pudiak CM
FAU - Barrot, Michel
AU  - Barrot M
FAU - Verhaagen, Joost
AU  - Verhaagen J
FAU - Nestler, Eric J
AU  - Nestler EJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Cell Line
MH  - Dependovirus/metabolism
MH  - Depression/*metabolism/physiopathology
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Exploratory Behavior
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Green Fluorescent Proteins
MH  - Humans
MH  - Immobilization
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Infusion Pumps
MH  - Kidney
MH  - Luminescent Proteins/metabolism
MH  - Male
MH  - Maze Learning
MH  - Nucleus Accumbens/*metabolism/virology
MH  - Proteins/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reaction Time
MH  - Receptor, trkB/genetics/metabolism
MH  - Signal Transduction/physiology
MH  - Swimming
MH  - Time Factors
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Ventral Tegmental Area/drug effects/*metabolism
EDAT- 2003/11/20 05:00
MHDA- 2003/12/31 05:00
CRDT- 2003/11/20 05:00
PHST- 2003/11/20 05:00 [pubmed]
PHST- 2003/12/31 05:00 [medline]
PHST- 2003/11/20 05:00 [entrez]
AID - S0006322303008692 [pii]
AID - 10.1016/j.biopsych.2003.08.003 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2003 Nov 15;54(10):994-1005. doi: 
      10.1016/j.biopsych.2003.08.003.