Document Detail

Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) microinfusions into the nucleus accumbens shell or ventral tegmental area attenuate the reinforcing effects of nicotine in rats.
MedLine Citation:
PMID:  21896278     Owner:  NLM     Status:  MEDLINE    
Systemic administration of the mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) was previously shown to selectively attenuate nicotine self-administration without affecting food-maintained responding in rats. Glutamatergic neurotransmission in the ventral tegmental area (VTA) and nucleus accumbens (NAcc) shell plays an important role in the reinforcing effects of nicotine. To determine the brain sites that may mediate the systemic effects of MPEP on nicotine self-administration, the present study investigated the effects of MPEP microinfusions into the VTA or the NAcc shell on nicotine and food self-administration in separate groups of rats. Administration of low MPEP doses (0, 0.5, 1, and 2 μg/0.5 μl/side) microinfused into the NAcc shell had no effect on nicotine self-administration, whereas higher MPEP doses (0, 10, 20, and 40 μg/0.5 μl/side) microinfused into the NAcc shell dose-dependently attenuated nicotine self-administration without affecting food-maintained responding. Microinfusions of MPEP into the VTA (0, 10, 20, and 40 μg/0.5 μl/side) significantly decreased both nicotine and food self-administration at 20 μg/0.5 μl/side but did not affect responding for either reinforcer at 40μg/0.5 μl/side. This lack of effect of 40 μg/0.5 μl/side MPEP on either nicotine or food self-administration when administered into the VTA may be attributable either to actions of MPEP at presynaptic mGlu5 receptors or at targets other than mGlu5 receptors. Importantly, anatomical control injections 2mm above the NAcc shell or the VTA using the most effective MPEP dose in the two regions did not result in attenuation of nicotine self-administration. In conclusion, MPEP microinfusions in the VTA or NAcc shell attenuates the reinforcing effects of nicotine possibly via blockade of mGlu5 receptors located in these regions.
Manoranjan S D'Souza; Athina Markou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-31
Journal Detail:
Title:  Neuropharmacology     Volume:  61     ISSN:  1873-7064     ISO Abbreviation:  Neuropharmacology     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-10-07     Completed Date:  2012-08-01     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1399-405     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Analysis of Variance
Conditioning, Operant / drug effects
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists / pharmacology*
Food Preferences / drug effects
Nicotine / administration & dosage*
Nicotinic Agonists / administration & dosage*
Nucleus Accumbens / drug effects*,  physiology
Pyridines / pharmacology*
Rats, Wistar
Reinforcement (Psychology)*
Reinforcement Schedule
Self Administration
Ventral Tegmental Area / drug effects*,  physiology
Grant Support
1R01DA11946/DA/NIDA NIH HHS; R01 DA011946/DA/NIDA NIH HHS; R01 DA011946-11/DA/NIDA NIH HHS; R56 DA011946/DA/NIDA NIH HHS
Reg. No./Substance:
0/6-methyl-2-(phenylethynyl)pyridine; 0/Excitatory Amino Acid Antagonists; 0/Nicotinic Agonists; 0/Pyridines; 54-11-5/Nicotine

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

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