The mGluR5 antagonist MPEP reduces the conditioned rewarding effects of cocaine but not other drugs of abuse.
We examined the ability of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective antagonist of the type 5 metabotropic glutamate receptor (mGluR5), to reduce the rewarding effects of various drugs of abuse in the conditioned place preference (CPP) paradigm. Mice were treated with MPEP (1, 5, and 20 mg/kg i.p.) 10 min prior to cocaine (15 mg/kg i.p.), D-amphetamine (2 mg/kg i.p.), nicotine (0.5 mg/kg i.p.), morphine (5 mg/kg i.p.), or ethanol (2 g/kg i.p.) on 3 successive days of CPP conditioning trials. MPEP pretreatment dose-dependently reduced the development of CPP for cocaine only. When tested alone at the doses effective in reducing CPP, MPEP produced neither a place preference nor aversion. These data provide further support for a role of the mGluR5 receptor in the rewarding effects of cocaine.
McGeehan
Andrew J
AJ
Department of Neurology, University of California at San Francisco, Emeryville, California 94608, USA.
Olive
M Foster
MF
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012201:Reward
D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; D013287:Illicit Drugs; D009294:Narcotics; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000431:Ethanol; D009538:Nicotine; D009020:Morphine; C121465:6-methyl-2-(phenylethynyl)pyridine; D000661:Amphetamine; D003042:Cocaine