Abstract:
PURPOSE:The present study was undertaken to clarify the effects of (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), a metabotropic glutamate receptor (mGluR) 1 antagonist, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a mGluR2/3 agonist, and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a mGluR4/8 agonist, on pentetrazol-induced kindled seizures. METHODS:Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. To induce kindling, pentetrazol at a dose of 40 mg/kg was injected once every 48 h. Behavioral and electroencephalographic seizures were monitored for 20 min following pentetrazol administration. Fully kindled mice were used for pharmacologic studies. RESULTS:Intracerebroventricular injection of AIDA and L-AP4 showed significant inhibitory effects on pentetrazol-induced kindled seizures. In addition, simultaneous use of AIDA and (2R,4R)-APDC or L-AP4 caused more potent inhibition of seizure activities. The inhibitory effect of AIDA on pentetrazol-induced kindled seizures was antagonized by (RS)-3,5-dihydroxyphenylglycine ((RS)-3,5-DHPG), a group I mGluR agonist; (2S)-a-ethylglutamic acid (EGLU), a group II mGluR antagonist; and (RS)-α-methyl-4-phosphonophenylglycine (MPPG), a group III mGluR antagonist. On the other hand, the inhibitory effect of L-AP4 was antagonized only by MPPG. DISCUSSION:It is proposed that mGluR1 antagonists and mGluR4/8 agonists show anticonvulsive effects on pentetrazol-induced kindled seizures. Furthermore, it is also proposed that the simultaneous use of an mGluR1 antagonist and an mGluR2/3 or mGluR4/8 agonist is a potential novel therapeutic strategy in epileptic disorders.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Watanabe Y,Kaida Y,Fukuhara S,Takechi K,Uehara T,Kamei Cdoi
10.1111/j.1528-1167.2010.02764.xsubject
Has Abstractpub_date
2011-01-01 00:00:00pages
140-50issue
1eissn
0013-9580issn
1528-1167journal_volume
52pub_type
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