Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test

Eur J Pharmacol. 2004 Oct 6;501(1-3):121-5. doi: 10.1016/j.ejphar.2004.08.016.

Abstract

Glutamatergic abnormalities are involved in several psychiatric disorders. Clinical evidence demonstrates altered glutamatergic neurotransmission in patients suffering from obsessive-compulsive disorder. MGS0039, (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid, is a novel group II metabotropic glutamate (mGlu) receptor antagonist. We examined MGS0039's potential anti-obsessive-compulsive disorder activity, using the marble-burying behavior test as a model of obsessive-compulsive disorder. MGS0039 as well as LY341495 ((2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycycloprolyl)glycine), another group II mGlu receptor antagonist, inhibited marble-burying behavior. We also demonstrated that this effect was significantly attenuated by a group II mGlu receptor agonist. This data indicates that group II mGlu receptor antagonists may exert anti-obsessive-compulsive disorder effects in clinical use.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anti-Anxiety Agents / therapeutic use
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged Bicyclo Compounds / therapeutic use
  • Dicarboxylic Acids / pharmacology*
  • Dicarboxylic Acids / therapeutic use
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Male
  • Mice
  • Mice, Inbred ICR
  • Obsessive-Compulsive Disorder / drug therapy
  • Obsessive-Compulsive Disorder / psychology
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / physiology

Substances

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