The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates conditioned place preference induced by various addictive and non-addictive drugs in rats.
We have recently reported that the metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates acquisition of conditioned place preference (CPP) induced by heroin and ketamine. The present study investigated to what extent this effect of MPEP can be generalized to other classes of drugs, such as the stimulants nicotine and cocaine, and to drugs that produce CPP in the rat despite a lack of abuse potential in humans, such as buspirone and clonidine. Adult male Sprague Dawley rats were subjected to a standard unbiased CPP protocol (six conditioning sessions lasting 20 minutes for nicotine and 40 minutes for the other compounds). Rats were conditioned with either nicotine (0.05-0.2 mg/kg, subcutaneously), cocaine [1-10 mg/kg, intraperitoneally (i.p.)], buspirone (0.3-3 mg/kg, i.p.) or clonidine (0.2-0.6 mg/kg, i.p.) in combination with MPEP (0 or 10 mg/kg, i.p.). For nicotine and cocaine, the minimal effective dose to induce CPP was lowered by pre-treatment with MPEP. While buspirone and clonidine did not induce CPP when given alone (i.e. combined with MPEP vehicle), both compounds induced CPP after pre-treatment with MPEP. It is concluded that MPEP consistently potentiates acquisition of drug-induced reward, independent of the mechanism of action of the co-administered drug. We suggest that the proposed anti-abuse effect of MPEP may be due to a substitution-like effect.
Rutten
Kris
K
Department of Pharmacology, Aachen, Germany. kris.rutten@grunenthal.com
Van Der Kam
Elizabeth L
EL
De Vry
Jean
J
Bruckmann
Walter
W
Tzschentke
Thomas M
TM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002065:Buspirone / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D013287:Illicit Drugs / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012931:Social Environment; D019966:Substance-Related Disorders / Q000503:physiopathology*
C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D013287:Illicit Drugs; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D009538:Nicotine; C121465:6-methyl-2-(phenylethynyl)pyridine; D003042:Cocaine; D003000:Clonidine; D002065:Buspirone