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Alcoholism Clinical and Experimental Research
Article . 2007 . Peer-reviewed
License: Wiley Online Library User Agreement
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Article . 2008
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Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats

Authors: Sara Faccidomo; Clyde W. Hodge; Julie J. M. Grondin; Joyce Besheer;

Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats

Abstract

Background:  Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self‐administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement.Methods:  Alcohol‐preferring (P) rats were trained to self‐administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self‐administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance.Results:  The mGluR1 antagonist, 3,4‐dihydro‐2H‐pyrano[2,3]b quinolin‐7‐yl (cis‐4‐methoxycyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6‐methyl‐2‐(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose‐dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity.Conclusions:  Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self‐administer ethanol.

Keywords

Male, Motivation, Reinforcement Schedule, Alcohol Drinking, Dose-Response Relationship, Drug, Ethanol, Receptor, Metabotropic Glutamate 5, Motor Activity, Receptors, Metabotropic Glutamate, Choice Behavior, Rats, Alcoholism, Animals

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    97
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    Top 10%
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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
97
Top 10%
Top 10%
Top 10%
bronze
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