Psychopharmacology

, 186:587

An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats

Authors

  • Takao Yoshimizu
    • Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., Ltd.
  • Toshiharu Shimazaki
    • Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., Ltd.
  • Akie Ito
    • Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., Ltd.
    • Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research LaboratoriesTaisho Pharmaceutical Co., Ltd.
Original Investigation

DOI: 10.1007/s00213-006-0390-7

Cite this article as:
Yoshimizu, T., Shimazaki, T., Ito, A. et al. Psychopharmacology (2006) 186: 587. doi:10.1007/s00213-006-0390-7

Abstract

Rationale

Abnormalities of glutamatergic neurotransmission have been reportedly observed in psychiatric disorders. Previously, we demonstrated that (1R, 2R, 3R, 5R, 6R)-2-Amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039) is a selective antagonist for group II metabotropic glutamate receptors (mGluR2/3), and that it exerted antidepressant effects in some animal behavioral tests.

Objectives

In the present study, we provide additional evidence that MGS0039 exhibits antidepressant and anxiolytic effects in experimental rodent models, which are predictive of clinical efficacy.

Methods

The learned helplessness (LH) paradigm, which is a common model used to examine the depressive state, was used to assess antidepressant effects of MGS0039. Moreover, anxiolytic effects of MGS0039 were investigated in the conditioned fear stress (CFS) model, which represents emotional abnormality, including anxiety.

Results

Intraperitoneal administration of MGS0039 (10 mg/kg) to rats for 7 days elicited a significant reduction in escape failures in the LH paradigm. In addition, rats treated with MGS0039 (2 mg/kg) showed significantly attenuated freezing behavior in a CFS model, indicating the anxiolytic-like potential of MGS0039.

Conclusions

These results suggest that the blockade of mGluR2/3 with MGS0039 may be effective in the treatment of depressive and anxiety disorders.

Keywords

mGluR2/3Learned helplessnessConditioned fear stressDepressionAnxietyMGS0039

Copyright information

© Springer-Verlag 2006