Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression.
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.
Eisch
Amelia J
AJ
Department of Psychiatry, The University of Texas Southwestern Medical Center, Texas, Dallas 75390-9070, USA.
Bolaños
Carlos A
CA
de Wit
Joris
J
Simonak
Ryan D
RD
Pudiak
Cindy M
CM
Barrot
Michel
M
Verhaagen
Joost
J
Nestler
Eric J
EJ
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D000229:Dependovirus / Q000378:metabolism; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005106:Exploratory Behavior; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D007103:Immobilization; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007260:Infusion Pumps; D007668:Kidney; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000821:virology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013550:Swimming; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; D011506:Proteins; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D020813:Receptor, trkB