Participation of metabotropic glutamate receptors in pentetrazol-induced kindled seizure.

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.

• Authors: Yusuke Watanabe, Yuko Kaida, Satoko Fukuhara, Kenshi Takechi, Takashi Uehara, Chiaki Kamei
• Journal: Epilepsia (Epilepsia) Vol. 52 Issue 1 Pg. 140-50 (Jan 2011) ISSN: 1528-1167 [Electronic] United States
• PMID: 21054350 (Publication Type: Comparative Study, Journal Article)
• Copyright: Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Chemical References

• Receptors, Metabotropic Glutamate
• Pentylenetetrazole

Topics

• Animals
• Electroencephalography (drug effects, methods)
• Kindling, Neurologic (drug effects, physiology)
• Male
• Mice
• Mice, Inbred ICR
• Pentylenetetrazole (toxicity)
• Receptors, Metabotropic Glutamate (physiology)
• Seizures (chemically induced, metabolism, physiopathology)