Alcohol and alcoholism (Oxford, Oxfordshire) · 2005
Effects of a metabotropic, mglu5, glutamate receptor antagonist on ethanol consumption by genetic drinking rats.
Сравнительное исследованиеСтатьяНазвание и аннотация: Перевод в очереди
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McMillen Brian A, Crawford Monica S, Kulers Cortney M, Williams Helen L
Аннотация
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.
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.
Предметные рубрики MeSH
Alcohol DeterrentsAlcohol DrinkingAnimalsAnti-Anxiety AgentsArousalDose-Response Relationship, DrugEatingEthanolFearFemaleGenotypeInjections, IntraperitonealInjections, SubcutaneousMaleMaze LearningPyridinesRatsRats, Inbred StrainsRats, Sprague-DawleyRats, WistarReceptor, Metabotropic Glutamate 5Receptors, Metabotropic Glutamate