Abstract:
: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 gamma-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 GABA(A) receptor antagonist, bicuculline and a GABA(C) 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 GABA(A) and GABA(C) receptors.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Watanabe Y,Kaida Y,Takechi K,Kamei Cdoi
10.1248/bpb.33.647subject
Has Abstractpub_date
2010-01-01 00:00:00pages
647-52issue
4eissn
0918-6158issn
1347-5215pii
JST.JSTAGE/bpb/33.647journal_volume
33pub_type
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