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Alcohol and Alcoholism Advance Access originally published online on September 26, 2005
Alcohol and Alcoholism 2005 40(6):494-497; 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

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

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

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

* Author to whom correspondence should be addressed at: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA. Tel.: +1 252 744 2758; Fax: +1 252 744 3203; E-mail: mcmillenb{at}mail.ecu.edu

(Received 18 March 2005; first review notified 31 May 2005; in final revised form 29 July 2005; accepted 29 July 2005)

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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