title: Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039.
abstract: We have previously reported that MGS0039, a novel antagonist of group II metabotropic glutamate receptors (mGluRs), exerts antidepressant-like effects in experimental animal models. Recent studies suggest that the behavioral effects of chronic antidepressant treatment are mediated by the stimulation of neurogenesis in the hippocampus. In the present study, we examined the effects of MGS0039 on cell proliferation in the adult mouse hippocampus. MGS0039 (5 or 10mg/kg) or fluvoxamine was administered chronically to male ICR mice over a period of 14 days. Multiple bromodeoxyuridine (BrdU) administrations were performed after the last drug injection to label dividing cells. Immunohistochemical analyses after BrdU injections revealed that chronic MGS0039 treatment enhanced BrdU-positive cells in the dentate gyrus ( approximately 62% increase) in the same manner as chronic fluvoxamine treatment. This is the first in vivo study to demonstrate an increase in cell proliferation following a blockade of group II mGluRs. These findings raise the possibility that MGS0039 may exert antidepressant-like effects by modulating cell proliferation in the hippocampus.
authors.affiliation: Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan. takao.yoshimizu@po.rd.taisho.co.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Yoshimizu
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Chaki
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013997:Time Factors
chemical_list: C483757:2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid; D000928:Antidepressive Agents; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D005456:Fluorescent Dyes; D018094:Receptors, Metabotropic Glutamate; D004247:DNA; D001973:Bromodeoxyuridine; D016666:Fluvoxamine