Anticonvulsant Effect of (RS)-1-Aminoindan-1,5-dicarboxylic Acid on Pentetrazol-Induced Kindled Seizures in Mice
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概要
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The present study was undertaken to clarify the effect of group I metabotropic glutamate receptor (mGluR) antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on pentetrazol-induced kindled seizures. The mechanism of the anticonvulsant effect of AIDA was also studied. Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. In order to induce kindling, pentetrazol at a dose of 40 mg/kg was injected intraperitoneally once every 48 h. Behavioral and electroencephalographic (EEG) seizures were observed for 20 min following pentetrazol administration. Intracerebroventricular (i.c.v.) injection of AIDA (1000 nmol/site) resulted in a significant inhibitory effect on pentetrazol-induced kindled seizures, and this effect was antagonized by a group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-3,5-DHPG). The effect of AIDA (200 nmol/site) on pentetrazol-induced kindled seizures was augmented by the simultaneous use of γ-aminobutyric acid (GABA) mimetic drugs, such as NNC-711 and diazepam. Moreover, the effect of AIDA (1000 nmol/site) on pentetrazol-induced kindled seizures was antagonized by a GABAA receptor antagonist, bicuculline and a GABAC receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA). It can be concluded that AIDA had an anticonvulsant effect on pentetrazol-induced kindled seizures, which was partially mediated by the GABAergic mechanism through GABAA and GABAC receptors.
著者
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Watanabe Yusuke
Department Of Cardiology Sakakibara Heart Institute
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Kamei Chiaki
Department Of Medical Pharmacology Okayama University Graduate School Of Medicine Dentistry And Phar
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Watanabe Yusuke
Department Of Medicinal Pharmacology Okayama University Graduate School Of Medicine Dentistry And Ph
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Takechi Kenshi
Department Of Medicinal Pharmacology Okayama University Graduate School Of Medicine Dentistry And Ph
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Kaida Yuko
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and
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Kamei Chiaki
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kaida Yuko
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Takechi Kenshi
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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