N-methyl-D-aspartate and group I metabotropic glutamate receptors are involved in the expression of ethanol-induced sensitization in mice.
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.
Kotlinska
Jolanta
J
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland. jolka.kotlinska@am.lublin.pl
Bochenski
Marcin
M
Danysz
Wojciech
W
D000077443:Acamprosate; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003517:Cyclopentanes / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
C502015:(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D003517:Cyclopentanes; D011725:Pyridines; D011804:Quinolines; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D013654:Taurine; D000431:Ethanol; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C114144:neramexane; D000077443:Acamprosate