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

Abstract

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. 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. 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%. 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.