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The Journal of Neuroscience, April 15, 2002, 22(8):3251-3261
Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression
Yukihiko Shirayama, Andrew C.-H. Chen, Shin Nakagawa, David S. Russell, and Ronald S. Duman Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508
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.
Key words: neurotrophin-3; nerve growth factor; dentate gyrus; learned helplessness; forced swim test; hippocampus; MAP kinase
Copyright © 2002 Society for Neuroscience 0270-6474/02/2283251-11$05.00/0
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