Journal
DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES
Volume 1139, Issue -, Pages 206-211Publisher
WILEY-BLACKWELL
DOI: 10.1196/annals.1432.034
Keywords
mGluR5 receptor; antagonist; methamphetamine; intravenous self-administration; reinforcement; rat; food
Categories
Funding
- NATIONAL INSTITUTE ON DRUG ABUSE [P50DA015369] Funding Source: NIH RePORTER
- NIDA NIH HHS [P50 DA015369, R01 DA025606] Funding Source: Medline
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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.
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