| 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. | |
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MedLine Citation:
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PMID: 20555310 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xinchun Jin; Svetlana Semenova; Li Yang; Robert Ardecky; Douglas J Sheffler; Russell Dahl; P Jeffrey Conn; Nicholas D P Cosford; Athina Markou |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-16 |
Journal Detail:
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Title: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Volume: 35 ISSN: 1740-634X ISO Abbreviation: Neuropsychopharmacology Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-16 Completed Date: 2010-12-06 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 8904907 Medline TA: Neuropsychopharmacology Country: United States |
Other Details:
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Languages: eng Pagination: 2021-36 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, University of California San Diego, La Jolla, 92093-0603, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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pharmacology Analysis of Variance Animals Behavior, Animal / drug effects Bicyclo Compounds, Heterocyclic / pharmacology Biphenyl Compounds / pharmacology* Brain / drug effects, metabolism Cell Line, Transformed Cocaine / administration & dosage* Cues* 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 Humans Indans / pharmacology* Male Rats Rats, Wistar Receptors, Metabotropic Glutamate / agonists, metabolism* Reinforcement Schedule Reward* Self Administration / methods Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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R01 DA011946-01A2/DA/NIDA NIH HHS; R01 DA023926/DA/NIDA NIH HHS; R01 DA023926-03/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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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; 50-36-2/Cocaine; 56-86-0/Glutamic Acid |
| Comments/Corrections | |
Comment In:
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Neuropsychopharmacology. 2010 Sep;35(10):2007-8
[PMID:
20711209
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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