Effects of MPEP on locomotion, sensitization and conditioned reward induced by cocaine or morphine.
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.
Herzig
Volker
V
Department of Neuropharmacology Zoological Institute, Faculty of Biology, University of Tübingen, Auf der Morgenstelle 28 E, 72076 Tübingen, Germany. schnakenstich@yahoo.com
Schmidt
Werner J
WJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000187:drug effects; D012201:Reward
D003042:Cocaine; D018691:Excitatory Amino Acid Antagonists; D009020:Morphine; D009292:Narcotic Antagonists; D009294:Narcotics; D011725:Pyridines; D018092:Kainic Acid Receptors; C121465:6-methyl-2-(phenylethynyl)pyridine