Selective mGlu5 receptor antagonist MTEP attenuates naloxone-induced morphine withdrawal symptoms

Pol J Pharmacol. 2004 Nov-Dec;56(6):863-6.

Abstract

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of drug addiction. The involvement of group I mGlu receptors in the mechanism of addiction has also been proposed. Given the recent discovery of selective and brain penetrable mGlu5 receptor antagonists, the effects of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) were evaluated in the naloxone-precipitated morphine withdrawal model. Experiments were performed on male C57BL/6J (20-25 g) mice. Mice were rendered morphine-dependent and withdrawal was precipitated with naloxone. Two hours and 15 min after the last dose of morphine, mice were injected with a mGlu5 receptor antagonist. MTEP (1-10 mg/kg) in a dose-dependent manner inhibited the naloxone-induced symptoms of morphine withdrawal in morphine-dependent mice, remaining without any effect on the locomotor activity of mice. The data suggest that selective mGlu5 receptor antagonists may play a role in the therapy of drug-dependence states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / adverse effects*
  • Morphine Dependence / drug therapy
  • Naloxone / pharmacology*
  • Narcotic Antagonists / pharmacology
  • Narcotics / adverse effects
  • Pyridines / therapeutic use*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Substance Withdrawal Syndrome / drug therapy*
  • Thiazoles / therapeutic use*

Substances

  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
  • Narcotic Antagonists
  • Narcotics
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Thiazoles
  • Naloxone
  • Morphine