Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat

Life Sci. 2003 Aug 15;73(13):1721-8. doi: 10.1016/s0024-3205(03)00509-5.

Abstract

The present study was designed to investigate the antipsychotic-like effects of selective group II metabotropic glutamate receptor (mGluR) agonists, 5-[2-[4-(6-fluoro-1H-indole-3-yl) piperidin-1-yl]ethyl]-4-(4-fluorophenyl)thiazole-2-carboxylic acid amide (MGS0008) and (1R, 2S, 5S, 6S)-2-amino-6-fluoro-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid monohydrate (MGS0028) on conditioned avoidance responses in rats. MGS0008 (1, 3 and 10 mg/kg, p.o.) and MGS0028 (0.3, 1 and 3 mg/kg, p.o.) significantly and reduced conditioned avoidance responses in a dose-dependent fashion. Similar effects were seen with LY418426 (0.3, 1 and 3 mg/kg, p.o.), but not with LY354740 (3, 10 and 30 mg/kg, p.o.), both of which are selective agonists for group II mGluR. Since this effect is seen with a wide range of antipsychotics, such as haloperidol and clozapine [Life Sciences 71 (2002) 947], group II mGluR agonists deserve further attention for possible antipsychotic activity.

MeSH terms

  • Administration, Oral
  • Animals
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / pharmacology*
  • Avoidance Learning / drug effects*
  • Behavior, Animal / drug effects*
  • Bridged Bicyclo Compounds / administration & dosage
  • Bridged Bicyclo Compounds / pharmacology*
  • Dicarboxylic Acids / administration & dosage
  • Dicarboxylic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / pharmacology*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists*

Substances

  • Antipsychotic Agents
  • Bridged Bicyclo Compounds
  • Dicarboxylic Acids
  • Excitatory Amino Acid Agonists
  • MGS 0008
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • eglumetad
  • MGS 0028