Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression.
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.
Shirayama
Yukihiko
Y
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
AC
Nakagawa
Shin
S
Russell
David S
DS
Duman
Ronald S
RS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004597:Electroshock; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004924:Escape Reaction / Q000187:drug effects; D006380:Helplessness, Learned; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D020932:Nerve Growth Factor / Q000008:administration & dosage; D020933:Neurotrophin 3 / Q000008:administration & dosage; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D020933:Neurotrophin 3; D016760:Proto-Oncogene Proteins c-fos; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases