Effect of the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) on the acute locomotor stimulant properties of cocaine, D-amphetamine, and the dopamine reuptake inhibitor GBR12909 in mice

Psychopharmacology (Berl). 2004 Jul;174(2):266-73. doi: 10.1007/s00213-003-1733-2.

Abstract

Rationale: Recent evidence suggests that, in addition to ascending monoaminergic systems, glutamate systems also play a role in psychostimulant-induced locomotor activity. The present study was conducted to examine the effects of the selective type-5 metabotropic glutamate receptor (mGluR5) antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) on the acute locomotor stimulant effects of cocaine, D-amphetamine, and the dopamine reuptake inhibitor GBR12909.

Methods: Male DBA/2J mice were treated with saline or MPEP (1, 5, 20 or 30 mg/kg i.p.) 10 min prior to the administration of cocaine (15 mg/kg or 30 mg/kg i.p.), D-amphetamine (3 mg/kg or 5 mg/kg i.p.) or GBR12909 (10 mg/kg or 20 mg/kg i.p.). Locomotor activity was then monitored in an open-field environment for 30 min. The effects of MPEP alone (1, 5, 20 and 30 mg/kg i.p.) on locomotor activity were also examined.

Results: MPEP dose dependently inhibited the acute locomotor stimulant effects of cocaine, D-amphetamine, and the 10-mg/kg dose of GBR12909. However, MPEP had no effect on the locomotor stimulant effects of the higher (20 mg/kg) dose of GBR12909. When tested alone, MPEP increased locomotor activity at doses of 5 mg/kg and 20 mg/kg.

Conclusions: Our data suggest that mGluR5 receptors not only mediate spontaneous locomotor activity in DBA/2J mice but also the acute locomotor stimulant effects of cocaine, D-amphetamine and lower doses of GBR12909. However, the fact that MPEP did not attenuate the locomotor stimulant effects of the high (20 mg/kg) dose of GBR12909 suggests complex interactions between metabotropic glutamate receptors, dopamine transporters and possibly other monoamines in the regulation of psychostimulant-induced locomotor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Cocaine / pharmacology*
  • Dopamine Agents / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Drug Interactions
  • Male
  • Mice
  • Mice, Inbred DBA
  • Motor Activity / drug effects*
  • Piperazines / pharmacology*
  • Pyridines / pharmacology*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*

Substances

  • Anti-Anxiety Agents
  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Grm5 protein, mouse
  • Piperazines
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • 6-methyl-2-(phenylethynyl)pyridine
  • vanoxerine
  • Amphetamine
  • Cocaine