Effects of a metabotropic, mglu5, glutamate receptor antagonist on ethanol consumption by genetic drinking rats.
OBJECTIVE
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.
McMillen
Brian A
BA
Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA. mcmillenb@mail.ecu.edu
Crawford
Monica S
MS
Kulers
Cortney M
CM
Williams
Helen L
HL
D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage; D005239:Fear / Q000187:drug effects*; D005260:Female; D005838:Genotype; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D000427:Alcohol Deterrents; D014151:Anti-Anxiety Agents; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000431:Ethanol; C121465:6-methyl-2-(phenylethynyl)pyridine