Document Detail

The mGluR2 positive allosteric modulator BINA decreases cocaine self-administration and cue-induced cocaine-seeking and counteracts cocaine-induced enhancement of brain reward function in rats.
MedLine Citation:
PMID:  20555310     Owner:  NLM     Status:  MEDLINE    
Metabotropic glutamate receptor 2/3 (mGluR2/3) agonists were shown previously to nonselectively decrease both cocaine- and food-maintained responding in rats. mGluR2 positive allosteric modulators (PAMs) may represent improved therapeutic compounds because of their modulatory properties and higher selectivity for mGluR2. We analyzed the effects of the selective, brain penetrant, and systemically active mGluR2 PAM potassium 3'-([(2-cyclopentyl-6-7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yl)oxy]methyl)biphenyl l-4-carboxylate (BINA) and the mGluR2/3 agonist LY379268 on intravenous cocaine self-administration and cocaine-seeking behavior in rats that had short (1 h, ShA) or long (6 h, LgA) access to cocaine. The effects of BINA on food responding and food-seeking behavior were also analyzed. Finally, we examined the effects of BINA on brain reward function and cocaine-induced reward enhancement using the intracranial self-stimulation procedure. BINA decreased cocaine self-administration in both ShA and LgA rats, with no effect on food self-administration. Alternatively, LY379268 nonselectively decreased both cocaine and food self-administration. BINA decreased cue-induced reinstatement of cocaine seeking with no effect on food seeking. The cocaine-induced enhancement of brain reward function was blocked by BINA, although the highest doses of BINA decreased brain reward function when administered alone, suggesting additive, rather than interactive, effects of BINA and cocaine. In conclusion, BINA attenuated the reinforcing and counteracted the reward-enhancing effects of cocaine and decreased cue-induced cocaine-seeking behavior, without affecting behaviors motivated by food reinforcement. The higher selectivity of BINA compared with an mGluR2/3 agonist for drug- vs food-motivated behaviors suggests a therapeutic role for mGluR2 PAMs for the treatment of cocaine addiction and possibly other drugs of abuse.
Xinchun Jin; Svetlana Semenova; Li Yang; Robert Ardecky; Douglas J Sheffler; Russell Dahl; P Jeffrey Conn; Nicholas D P Cosford; Athina Markou
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-16
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  35     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-12-06     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2021-36     Citation Subset:  IM    
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MeSH Terms
Amino Acids / pharmacology
Analysis of Variance
Behavior, Animal / drug effects
Bicyclo Compounds, Heterocyclic / pharmacology
Biphenyl Compounds / pharmacology*
Brain / drug effects,  metabolism
Cell Line, Transformed
Cocaine / administration & dosage*
Dopamine Uptake Inhibitors / administration & dosage*
Dose-Response Relationship, Drug
Drug Interactions
Excitatory Amino Acid Agonists / pharmacology*
Extinction, Psychological / drug effects
Feeding Behavior / drug effects
Glutamic Acid / metabolism
Indans / pharmacology*
Rats, Wistar
Receptors, Metabotropic Glutamate / agonists,  metabolism*
Reinforcement Schedule
Self Administration / methods
Time Factors
Grant Support
R01 DA011946/DA/NIDA NIH HHS; R01 DA011946-01A2/DA/NIDA NIH HHS; R01 DA023926/DA/NIDA NIH HHS; R01 DA023926/DA/NIDA NIH HHS; R01 DA023926-03/DA/NIDA NIH HHS; R01 NS031373/NS/NINDS NIH HHS
Reg. No./Substance:
0/Amino Acids; 0/Bicyclo Compounds, Heterocyclic; 0/Biphenyl Compounds; 0/Dopamine Uptake Inhibitors; 0/Excitatory Amino Acid Agonists; 0/Indans; 0/LY 379268; 0/Receptors, Metabotropic Glutamate; 0/biphenyl-indanone A; 0/metabotropic glutamate receptor 2; 3KX376GY7L/Glutamic Acid; I5Y540LHVR/Cocaine
Comment In:
Neuropsychopharmacology. 2010 Sep;35(10):2007-8   [PMID:  20711209 ]

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