Document Detail

mGluR5 antagonism attenuates methamphetamine reinforcement and prevents reinstatement of methamphetamine-seeking behavior in rats.
MedLine Citation:
PMID:  18800068     Owner:  NLM     Status:  MEDLINE    
Addiction to methamphetamine is a significant public health problem, and there are currently no pharmacological agents that are approved for the treatment of addiction to this powerful psychostimulant. Chronic methamphetamine use leads to cognitive dysfunction as well as numerous psychiatric, neurological, and cardiovascular complications. There is a growing body of literature implicating an important role for glutamate neurotransmission in psychostimulant addiction. In the present study, we examined the effects of the selective type 5 metabotropic glutamate receptor (mGluR5) antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) on intravenous self-administration of methamphetamine and reinstatement of methamphetamine-seeking behavior. Adult male Sprague-Dawley rats were trained to respond for intravenous methamphetamine (0.1 or 0.2 mg/kg per infusion) or food pellets and were subsequently administered vehicle or MTEP (0.3-3 mg/kg) before drug or food self-administration on a fixed-ratio 1 (FR1) schedule of reinforcement or a progressive ratio (PR) schedule of reinforcement. We also examined the effects of vehicle or MTEP (0.3-3 mg/kg) on cue- and drug-induced reinstatement of methamphetamine-seeking behavior as well as cue-induced reinstatement of food-seeking behavior. Our results show that MTEP dose dependently reduced the reinforcing effects of methamphetamine under FR1 and PR schedules of reinforcement without altering overall responding for food. MTEP also dose dependently prevented cue- and drug-induced reinstatement of methamphetamine-seeking behavior, but did not alter cue-induced reinstatement of food-seeking behavior. Together, these results indicate that mGluR5 receptors mediate methamphetamine reinforcement and methamphetamine-seeking behavior, and that pharmacological inhibitors of mGluR5 receptor function may represent a novel class of potential therapeutic agents for the treatment of methamphetamine addiction.
Justin T Gass; Megan P H Osborne; Noreen L Watson; Jordan L Brown; M Foster Olive
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-17
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  34     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-10     Completed Date:  2009-03-23     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  820-33     Citation Subset:  IM    
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MeSH Terms
Amphetamine-Related Disorders / drug therapy*
Analysis of Variance
Appetitive Behavior / drug effects
Behavior, Addictive / drug therapy*
Behavior, Animal / drug effects
Excitatory Amino Acid Antagonists / therapeutic use*
Methamphetamine / administration & dosage*
Pyridines / therapeutic use*
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Reinforcement Schedule
Self Administration
Thiazoles / therapeutic use*
Grant Support
Reg. No./Substance:
0/3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; 0/Excitatory Amino Acid Antagonists; 0/Pyridines; 0/Receptors, Metabotropic Glutamate; 0/Thiazoles; 44RAL3456C/Methamphetamine
Comment In:
Neuropsychopharmacology. 2009 Mar;34(4):817-9   [PMID:  19092781 ]

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