title: Role of BDNF/TrkB signaling in antidepressant-like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression.
abstract: We previously revealed that the activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor and mammalian target of rapamycin signaling contributed to the antidepressant-like effects of group II metabotropic glutamate (mGlu2/3) receptor antagonists, suggesting that the signaling pathway may be similar to the molecular mechanisms underlying the antidepressant-like action of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist that exertes rapid and sustained antidepressant effects in patients with depressive disorder. Although brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling reportedly participates in the antidepressant-like effects of ketamine, the involvement of BDNF/TrkB signaling in the action of mGlu2/3 receptor antagonists has not been investigated. We therefore examined whether the activation of BDNF/TrkB signaling is required for the antidepressant-like effects of LY341495, an mGlu2/3 receptor antagonist, in animal models of depression such as the tail suspension test (TST) and the novelty-suppressed feeding test (NSFT). The administration of LY341495 at 30 min prior to the test exerted antidepressant-like effects (acute effects) lasting for at least 24 h (sustained effects) when evaluated using the TST and NSFT. Pretreatment with K252a, a TrkB tyrosine kinase inhibitor, blocked the sustained, but not the acute, effects of LY341495. These results suggest that BDNF/TrkB signaling may be involved in the sustained antidepressant-like effects of LY341495, as observed for ketamine treatment.
authors.affiliation: Discovery Pharmacology I, Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koike
authors.forename: Kenichi
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Michihiko
authors.initials: M
authors.lastname: Iijima
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Chaki
mesh_terms: D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D020813:Receptor, trkB / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D020813:Receptor, trkB