Abstract
Effects of acamprosate and ionotropic uncompetitive N-methyl-D-aspartate receptor antagonists and group I metabotropic glutamatergic receptor antagonists on the expression of ethanol-induced sensitization were investigated in mice. The results indicated that acamprosate (200 and 400 mg/kg) and N-methyl-D-aspartate receptor antagonists, neramexane (10 and 20 mg/kg) and MK-801 (0.1 and 0.2 mg/kg), inhibited the expression of ethanol-induced sensitization. Acamprosate, but not the other compounds tested, also blocked the stimulant effect of acute injections of ethanol. Among the group I metabotropic glutamatergic receptor antagonists, only the metabotropic glutamatergic receptor 5 antagonist, MTEP (5, 10, and 20 mg/kg) showed an effect similar to the N-methyl-D-aspartate receptor antagonists. The metabotropic glutamatergic receptor 1 antagonist, EMQMCM (5, 10, and 20 mg/kg), however, potentiated the inhibitory effect of MK-801 on the expression of ethanol-induced sensitization. The findings indicate that glutamatergic neurotransmission is important in the ethanol-induced sensitization process, and suggest that co-administration of metabotropic glutamatergic receptor 1 antagonists and N-methyl-D-aspartate receptor antagonists may be useful in therapy for alcoholism.
MeSH terms
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Acamprosate
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Alcoholism / physiopathology*
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Animals
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Brain / drug effects
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Brain / physiopathology
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Cyclopentanes / pharmacology
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Dizocilpine Maleate / pharmacology
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Dose-Response Relationship, Drug
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Drug Synergism
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Ethanol / pharmacology*
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Glutamic Acid / physiology
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Male
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Mice
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Motor Activity / drug effects
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Motor Activity / physiology
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N-Methylaspartate / antagonists & inhibitors
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N-Methylaspartate / physiology*
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Pyridines / pharmacology
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Quinolines / pharmacology
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / physiology*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / physiology*
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Stereotyped Behavior / drug effects
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Stereotyped Behavior / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Taurine / analogs & derivatives
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Taurine / pharmacology
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Thiazoles / pharmacology
Substances
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(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate
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3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
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Cyclopentanes
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Pyridines
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Quinolines
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Receptors, Metabotropic Glutamate
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Receptors, N-Methyl-D-Aspartate
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Thiazoles
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metabotropic glutamate receptor type 1
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Taurine
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Ethanol
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Glutamic Acid
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N-Methylaspartate
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Dizocilpine Maleate
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neramexane
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Acamprosate