Document Detail

The group II metabotropic glutamate receptor agonist, LY379268, inhibits both cocaine- and food-seeking behavior in rats.
MedLine Citation:
PMID:  16703399     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Group II metabotropic glutamate receptor (mGluR2/3) agonists are proposed to serve as potential treatment for addiction. OBJECTIVES: The present study examined the hypothesis that mGluR2/3 agonists exert inhibitory effects on cocaine-induced reinstatement of cocaine-seeking. METHODS: Rats were trained to self-administer either cocaine or control reinforcer (food), then responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p. or 765 mg of food). In one experiment, rats were systemically pretreated with vehicle (Veh) or the mGluR2/3 agonist LY379268 (0.3, 1, or 3 mg/kg, i.p.) 30 min before the reinstatement test session. In a second experiment, Veh or LY379268 (0.05, 0.5, or 5 nmol/side) was microinjected into the nucleus accumbens core (NAc core) 5 min before the reinstatement test session. The effects of LY379268 on cocaine- and food-induced reinstatement on reward seeking were assessed. RESULTS: Both systemic and intra-NAc core pretreatment with LY379268 inhibited both cocaine- and food-seeking behavior. However, the effect of LY379268 appeared somewhat more effective for cocaine-seeking than food-seeking. CONCLUSIONS: These results support a potential therapeutic role for mGluR2/3 agonists on relapse of cocaine-seeking. However, doses that inhibited cocaine-seeking were only threefold lower than those inhibiting food-seeking, indicating possible unacceptable nonspecific effects. In addition, the NAc core is one site of action where the mGluR2/3 agonists elicit effects on reward-seeking behavior.
Jamie Peters; Peter W Kalivas
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-04-22
Journal Detail:
Title:  Psychopharmacology     Volume:  186     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-16     Completed Date:  2006-10-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  143-9     Citation Subset:  IM    
Department of Neurosciences, Medical University of South Carolina, Charleston, SC, 29425, USA.
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MeSH Terms
Amino Acids* / administration & dosage,  pharmacology,  therapeutic use
Behavior, Animal / drug effects*
Bicyclo Compounds, Heterocyclic* / administration & dosage,  pharmacology,  therapeutic use
Cocaine* / administration & dosage,  adverse effects
Cocaine-Related Disorders / metabolism,  prevention & control*,  psychology
Dose-Response Relationship, Drug
Feeding Behavior / drug effects*
Nucleus Accumbens / drug effects,  metabolism
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / agonists*
Self Administration
Grant Support
Reg. No./Substance:
0/Amino Acids; 0/Bicyclo Compounds, Heterocyclic; 0/LY 379268; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 2; 50-36-2/Cocaine

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