Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039

doi:10.1016/j.bbrc.2004.01.073

Biochemical and Biophysical Research Communications

Volume 315, Issue 2, 5 March 2004, Pages 493-496

https://doi.org/10.1016/j.bbrc.2004.01.073 Get rights and content

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 10 mg/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 (∼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.

Section snippets

Materials and methods

Experimental animals. Male ICR mice, 8–10 weeks old (Charles River, Japan), were used for this study. All mice were housed in groups of 10 per cage, under standard conditions; room temperature (23 ± 3 °C); light–dark cycle (light phase 7:00–19:00). The mice were given free access to food and water except during the experiment. This study was conducted with the approval of Taisho Pharmaceutical Co., Ltd. Animal Care Committee.

Chemicals and drug administration. For chronic dosing, MGS0039 (5 or 10

Results and discussion

BrdU-labeled nuclei of proliferating cells were frequently observed in clusters, localized in the subgranular zone of the hippocampus in all treated mice (Fig. 1). In chronic fluvoxamine-treated animals, the total number of BrdU-positive cells in the dentate gyrus and hilus was 2019 ± 59 (mean ± SEM) compared with 1499 ± 75 in the vehicle group, which corresponds to a significant increase (35%) (p<0.001). Interestingly, chronic administration of MGS0039 at 5 and 10 mg/kg promoted progenitor cell

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Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039

Abstract

Section snippets

Materials and methods

Results and discussion

Neuropharmacology

Neuropharmacology

Neuropharmacology

Pharmacology and functions of metabotropic glutamate receptors

Annu. Rev. Pharmacol. Toxicol.

Hippocampal volume reduction in major depression

Am. J. Psychiatry

Neurogenesis in the adult human hippocampus

Nat. Med.

Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation

J. Neurosci.