A role for mGluR5 receptors in intravenous methamphetamine self-administration.
Selective antagonists of the mGluR5 receptor attenuate rewarding and reinforcing effects of various drugs of abuse, including alcohol, nicotine, and cocaine. However, the ability of mGluR5 antagonists to alter the reinforcing effects of methamphetamine has not yet been explored. In this study, male Sprague-Dawley rats were trained to perform an operant lever-pressing task in order to obtain intravenous infusions of methamphetamine (0.2 mg/kg/infusion) or presentation of food pellets on a fixed ratio (FR1) schedule of reinforcement. After stabilization of methamphetamine or food self-administration, the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]pyridine (MTEP; 0.3, 1.0, or 3.0 mg/kg i.p.) or vehicle were administered to the animals in a randomized counterbalanced cross-over design. MTEP at doses of 1.0 and 3.0 mg/kg significantly reduced methamphetamine self-administration by 26 and 36%, respectively, but did not alter food reinforcement at any dose tested. These data suggest that mGluR5 receptors are involved in the reinforcing effects of methamphetamine, and that antagonists of this receptor may serve as novel pharmacologic agents for the treatment of addiction to methamphetamine.
Osborne
Megan P H
MP
Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Olive
M Foster
MF
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013844:Thiazoles / Q000378:metabolism
C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; D008694:Methamphetamine