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

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.

• Authors: Takao Yoshimizu, Toshiharu Shimazaki, Akie Ito, Shigeyuki Chaki
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 186 Issue 4 Pg. 587-93 (Jul 2006) ISSN: 0033-3158 [Print] Germany
• PMID: 16612616 (Publication Type: Journal Article)

Chemical References

• 2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid
• Anti-Anxiety Agents
• Antidepressive Agents
• Bridged Bicyclo Compounds
• Dicarboxylic Acids
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 2
• metabotropic glutamate receptor 3

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Antidepressive Agents (pharmacology)
• Avoidance Learning (drug effects)
• Behavior, Animal (drug effects)
• Bridged Bicyclo Compounds (pharmacology)
• Conditioning, Classical (drug effects)
• Dicarboxylic Acids (pharmacology)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Male
• Models, Animal
• Motor Activity (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Metabotropic Glutamate (antagonists & inhibitors)