Behavioral characterization of the mGlu group II/III receptor antagonist, LY-341495, in animal models of anxiety and depression

Eur J Pharmacol. 2008 Sep 11;592(1-3):96-102. doi: 10.1016/j.ejphar.2008.06.089. Epub 2008 Jul 2.

Abstract

There is a growing body of evidence indicating that stimulation of metabotropic glutamate type II receptors (mGlu2/3) reduces anxiety in laboratory animals and humans. Surprisingly, it was reported that mGlu2/3 receptor antagonists have antidepressant- and anxiolytic-like activities in laboratory animal studies as well. The present study aimed to resolve this controversy by characterizing behavioral effects of a selective mGlu2/3 receptor antagonist, LY-341495, in a variety of animal models sensitive to clinically used anxiolytic and antidepressant agents. In agreement with previous reports, LY-341495 (0.3-3 mg/kg, i.p.) reduced immobility in the mouse forced swim test. LY-341495 was also effective in the marble burying test in mice, although similar effects were observed after administration of various drugs including methamphetamine. Further, LY-341495 had no effects in the elevated plus maze and stress-induced hyperthermia tests in mice, as well as on punished drinking (Geller-Seifter's test) and differential reinforcement of low rates of responding (DRL) in rats. It is concluded that behavioral profile of mGlu2/3 receptor antagonists as represented by LY-341495 is different from that of conventional anxiolytic and antidepressant drugs.

MeSH terms

  • Amino Acids / pharmacology*
  • Amphetamine / pharmacology
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Antidepressive Agents, Second-Generation / pharmacology
  • Anxiety / drug therapy*
  • Anxiety / psychology*
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / pharmacology
  • Conditioning, Operant / drug effects
  • Darkness
  • Depression / drug therapy*
  • Depression / psychology*
  • Diazepam / pharmacology
  • Fever / physiopathology
  • Fever / psychology
  • Fluoxetine / pharmacology
  • Light
  • Male
  • Mice
  • Paroxetine / pharmacology
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Reinforcement Schedule
  • Stress, Psychological / physiopathology
  • Stress, Psychological / psychology
  • Xanthenes / pharmacology*

Substances

  • Amino Acids
  • Anti-Anxiety Agents
  • Antidepressive Agents, Second-Generation
  • Central Nervous System Stimulants
  • LY 341495
  • Receptors, Metabotropic Glutamate
  • Xanthenes
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Fluoxetine
  • Paroxetine
  • Amphetamine
  • Diazepam