The mGlu5 receptor antagonist MTEP attenuates opiate self-administration and cue-induced opiate-seeking behaviour in mice

Drug Alcohol Depend. 2012 Jun 1;123(1-3):264-8. doi: 10.1016/j.drugalcdep.2011.11.002. Epub 2011 Nov 29.

Abstract

The mGlu5 receptor (mGluR5) has been implicated in the rewarding effect of various drugs of abuse and drug-seeking behaviour. In the present study we investigated the impact of antagonism of mGluR5 with the selective negative allosteric, modulator 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) on operant self-administration of morphine as well as cue-induced drug-seeking in adult CD1 mice. Administration of MTEP (20 mg/kg, i.p.) attenuated operant responding for morphine (0.1 mg/kg/infusion) and cue-induced morphine-seeking after a period of forced abstinence. Collectively, these data implicate mGluR5 in the reinforcing effects of opiates and support the proposition that mGluR5 is a potential therapeutic target for treatment of drug addiction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid*
  • Analysis of Variance
  • Animals
  • Conditioning, Operant
  • Cues*
  • Dose-Response Relationship, Drug
  • Injections, Intravenous
  • Male
  • Mice
  • Morphine / administration & dosage
  • Morphine / pharmacology
  • Motor Activity / drug effects
  • Narcotics / administration & dosage
  • Narcotics / pharmacology
  • Opioid-Related Disorders / prevention & control*
  • Opioid-Related Disorders / psychology*
  • Piperidines / pharmacology*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Reinforcement, Psychology
  • Self Administration
  • Substance Abuse, Intravenous / psychology
  • Thiazoles / pharmacology*

Substances

  • 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine
  • Analgesics, Opioid
  • Grm5 protein, mouse
  • Narcotics
  • Piperidines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Thiazoles
  • Morphine