Effects of MPEP on locomotion, sensitization and conditioned reward induced by cocaine or morphine

Neuropharmacology. 2004 Dec;47(7):973-84. doi: 10.1016/j.neuropharm.2004.07.037.

Abstract

Exposure to environmental cues is considered a major cause of relapse in detoxified addicts. Recent findings showed an involvement of glutamate in cue-induced relapse and suggest that subtype 5 of metabotropic glutamate receptors (mGluR5) is involved in conditioned drug-reward. The present study applied the conditioned place preference (CPP) paradigm to examine the involvement of mGluR5 in cocaine- and morphine-induced behaviours. Results of previous mice-studies were extended into rats by using the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). As a result, the evaluated behavioural parameters were dose-relatedly affected by MPEP. Low-dosed MPEP (10 mg/kg, i.p.) did not affect spontaneous locomotion, reduced cocaine-induced hyperlocomotion and produced sensitized locomotion, while showing no effect on sensitized locomotion induced by repeated cocaine or morphine. Low-dosed MPEP did not genuinely block development of cocaine- and morphine-CPP, but rendered CPP expression state-dependent. The medium MPEP-dose (30 mg/kg) was most effective in reducing spontaneous locomotion. The high MPEP-dose (50 mg/kg) was most effective in reducing both body-weight and morphine-CPP expression. Cocaine-CPP expression was not affected by any MPEP-dose. In conclusion, mGluR5 are involved in modulation of spontaneous and cocaine-induced locomotion, in state-dependent learning and in expression of morphine-CPP. Thus, MPEP may be beneficial for relapse prevention in morphine-addicts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cocaine / antagonists & inhibitors
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Learning / drug effects
  • Male
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Motor Activity / drug effects*
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacology*
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Kainic Acid / drug effects
  • Reward

Substances

  • Excitatory Amino Acid Antagonists
  • Gluk1 kainate receptor
  • Narcotic Antagonists
  • Narcotics
  • Pyridines
  • Receptors, Kainic Acid
  • Morphine
  • 6-methyl-2-(phenylethynyl)pyridine
  • Cocaine