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PMID: 11943826 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 8 ·2002-04-15 ·Pages 3251-61

Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS

Abstract

Previous studies demonstrated that antidepressant treatment increases the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampus. The present study was conducted to test the hypothesis that BDNF in the hippocampus produces an antidepressant effect in behavioral models of depression, the learned helplessness (LH) and forced swim test (FST) paradigms. A single bilateral infusion of BDNF into the dentate gyrus of hippocampus produced an antidepressant effect in both the LH and FST that was comparable in magnitude with repeated systemic administration of a chemical antidepressant. These effects were observed as early as 3 d after a single infusion of BDNF and lasted for at least 10 d. Similar effects were observed with neurotrophin-3 (NT-3) but not nerve growth factor. Infusions of BDNF and NT-3 did not influence locomotor activity or passive avoidance. The results provide further support for the hypothesis that BDNF contributes to the therapeutic action of antidepressant treatment.

MeSH Terms
Animals Behavior, Animal/drug effects Brain-Derived Neurotrophic Factor/administration & dosage Dentate Gyrus/drug effects,enzymology Depression/drug therapy Disease Models, Animal Electroshock Enzyme Inhibitors/administration & dosage Escape Reaction/drug effects Helplessness, Learned Hippocampus/drug effects,enzymology Immunohistochemistry Male Microinjections Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism Motor Activity/drug effects Nerve Growth Factor/administration & dosage Neurotrophin 3/administration & dosage Proto-Oncogene Proteins c-fos/metabolism Rats Rats, Sprague-Dawley Reaction Time/drug effects Spatial Behavior/drug effects
Chemicals
Brain-Derived Neurotrophic Factor Enzyme Inhibitors Neurotrophin 3 Proto-Oncogene Proteins c-fos Nerve Growth Factor Mitogen-Activated Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shirayama Yukihiko
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Chen Andrew C-H
Nakagawa Shin
Russell David S
Duman Ronald S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026292
Published
2002-04-15
Pages
3251-61
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6757539
Subset
IM
Grants
NIMH NIH HHS · P01 MH025642 · United States
NIMH NIH HHS · MH45481 · United States
NIMH NIH HHS · R37 MH045481 · United States
NIMH NIH HHS · 2PO1 MH25642 · United States
NIMH NIH HHS · R01 MH045481 · United States
External Links
PubMed source DOI: 20026292 PMC Full Text View journal details
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