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Alcohol and Alcoholism Advance Access published online on September 26, 2005
Alcohol and Alcoholism, doi:10.1093/alcalc/agh200
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© The Author 2005. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved
Received March 18, 2005
Revised July 29, 2005
Accepted July 29, 2005

Article

EFFECTS OF A METABOTROPIC, MGLU5, GLUTAMATE RECEPTOR ANTAGONIST ON ETHANOL CONSUMPTION BY GENETIC DRINKING RATS

BRIAN A. McMILLEN 1*, MONICA S. CRAWFORD 1, CORTNEY M. KULERS 1, and HELEN L. WILLIAMS 1

1 Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA

* To whom correspondence should be addressed.
BRIAN A. McMILLEN, E-mail: mcmillenb{at}mail.ecu.edu


  Abstract

Aims: To compare the effect of an antagonist of the mGlu5 glutamate receptor, 2-methyl-6-(phenylethynyl)pyridine (MPEP) on a test for anxiety and on the volitional consumption of ethanol. Methods: The test for anxiety was placement of a Sprague-Dawley rat for a 5 min observation period in an elevated plus-maze. Volitional consumption of ethanol in a two-choice paradigm was determined for male and female myers high ethanol-preferring rats after a 10-day ‘step-up’ test of 3-30% v/v ethanol vs water used to determine each rat's preferred concentration of ethanol. Each rat received a 4-day baseline period, 3-days of drug injection b.i.d., and a 4-day post-treatment period and then rotated to a different dose of drug or vehicle. Results: The effects of MPEP on elevated plus-maze activity were not significant at doses up to 3.0 mg/kg subcutaneously 60 min. before observation. There was a dose-dependent, 0.3, 1.0, 3.0 mg/kg, decrease in consumption of preferred concentrations of ethanol, along with a decrease in the proportion of ethanol consumed to total fluids consumed. The 3.0 mg/kg b.i.d. dose of MPEP reduced consumption by 57%, proportion by 45%, and food intake by 10%. Conclusions: MPEP did not appear to have an anti-anxiety effect, but volitional drinking in a genetic model was reduced. The mGlu5 receptor may provide a target for drug action to reduce the consumption of ethanol.


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