Document Detail

Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator.
MedLine Citation:
PMID:  22820868     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Methamphetamine (METH) is a highly potent and addictive psychostimulant with severe detrimental effects to the health of users. Currently, METH addiction is treated with a combination of cognitive and behavioral therapies, but these traditional approaches suffer from high relapse rates. Furthermore, there are currently no pharmacological treatment interventions approved by the FDA specifically for the treatment of METH addiction.
OBJECTIVES: Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) have shown promise in significantly attenuating drug self-administration and drug-seeking in reinstatement paradigms. However, studies assessing the potential efficacy of mGluR5 NAMs that have been tested in human subjects are lacking. The current study sought to assess the effect of the mGluR5 NAM fenobam on METH-seeking behavior.
METHODS: Rats were trained to self-administer METH (0.05 mg/kg i.v.), and following extinction, tested for effects of fenobam (5, 10, or 15 mg/kg intraperitoneal) on cue- and drug-induced reinstatement of METH-seeking. To determine if fenobam also alters reinstatement of seeking of natural reinforcers, separate groups of rats were trained to self-administer sucrose or food pellets and were tested for the effects of fenobam on cue-induced reinstatement of sucrose- and food-seeking.
RESULTS: Fenobam attenuated drug- and cue-induced reinstatement of METH-seeking behavior at doses of 10 and 15 mg/kg. Fenobam also attenuated cue-induced reinstatement of sucrose- and food-seeking at all doses tested.
CONCLUSIONS: The mGluR5 NAM fenobam attenuates the reinstatement of METH-seeking behavior, but these effects may be due to nonspecific suppression of general appetitive behaviors.
Lucas R Watterson; Peter R Kufahl; Natali E Nemirovsky; Kaveish Sewalia; Lauren E Hood; M Foster Olive
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-21
Journal Detail:
Title:  Psychopharmacology     Volume:  225     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-06-10     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  151-9     Citation Subset:  IM    
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MeSH Terms
Allosteric Regulation
Dose-Response Relationship, Drug
Feeding Behavior
Imidazoles / administration & dosage,  pharmacology*
Methamphetamine / administration & dosage*
Rats, Sprague-Dawley
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / drug effects*,  metabolism
Reinforcement Schedule
Self Administration
Sucrose / administration & dosage*
Grant Support
Reg. No./Substance:
0/GRM5 protein, human; 0/Grm5 protein, rat; 0/Imidazoles; 0/Receptor, Metabotropic Glutamate 5; 0/Receptors, Metabotropic Glutamate; 07O6708M02/fenobam; 44RAL3456C/Methamphetamine; 57-50-1/Sucrose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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