The mGlu(2/3) receptor agonist LY379268 selectively blocks amphetamine ambulations and rearing

Eur J Pharmacol. 2000 Jul 21;400(2-3):221-4. doi: 10.1016/s0014-2999(00)00423-4.

Abstract

We have previously reported that the specific group II metabotropic glutamate receptor agonist LY379268 inhibited phencyclidine (PCP)-induced motor activations in rats, but had mixed effects on behaviors produced by amphetamine. Here, LY379268 (1 mg/kg subcutaneous (s.c.)) attenuated amphetamine-induced ambulations and rearing but did not alter amphetamine-evoked fine motor movements. Consistent with a mechanism involving mGlu(2/3) receptors, the inhibitory actions of LY379268 on ambulations and rearing were reversed by LY341495, a mGlu(2/3) receptor antagonist. These data further suggest antipsychotic actions of mGlu(2/3) receptor agonists with a low propensity for extra-pyramidal side effects.

MeSH terms

  • Amino Acids / antagonists & inhibitors
  • Amino Acids / pharmacology*
  • Amphetamine / antagonists & inhibitors*
  • Amphetamine / pharmacology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / antagonists & inhibitors
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Male
  • Motor Activity / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / physiology
  • Stereotyped Behavior / drug effects
  • Xanthenes / pharmacology

Substances

  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • LY 341495
  • LY 379268
  • Receptors, Metabotropic Glutamate
  • Xanthenes
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Amphetamine