Morphine conditioned reward is inhibited by MPEP, the mGluR5 antagonist

Neuropharmacology. 2002 Dec;43(8):1210-7. doi: 10.1016/s0028-3908(02)00309-x.


In the present study we examined the effect of MPEP [2-methyl-6-(phenylethynyl)-pyridine] a potent, selective and systemically active metabotropic glutamate receptor (mGluR) type I (subtype mGluR5) antagonist on conditioned morphine reward in mice. In an unbiased version of conditioned place preference (CPP) paradigm, single conditioning with 10 mg/kg of morphine produced reliable place preference. MPEP at 30, but not 10 mg/kg significantly inhibited the acquisition as well as expression of morphine-induced CPP, but it neither produced place preference or aversion, nor affected locomotor activity of mice. Effects of MPEP on learning and memory were studied in the elevated plus maze model of spatial learning. In contrast to 0.1 mg/kg of MK-801, which inhibited the acquisition of this task, 30 mg/kg of MPEP affected neither learning nor memory retrieval. These data suggest that mGluR5 may be involved in conditioned morphine reward.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Excitatory Amino Acid Antagonists
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / pharmacology*
  • Pyridines / pharmacology*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / physiology
  • Reward*


  • Excitatory Amino Acid Antagonists
  • Grm5 protein, mouse
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Morphine
  • 6-methyl-2-(phenylethynyl)pyridine