PT  - JOURNAL ARTICLE
AU  - Alfonso Tortorella
AU  - Toivo Halonen
AU  - Niaz Sahibzada
AU  - Karen Gale
TI  - A Crucial Role of the α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid Subtype of Glutamate Receptors in Piriform and Perirhinal Cortex for the Initiation and Propagation of Limbic Motor Seizures
DP  - 1997 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1401--1405
VI  - 280
IP  - 3
4099  - http://jpet.aspetjournals.org/content/280/3/1401.short
4100  - http://jpet.aspetjournals.org/content/280/3/1401.full
SO  - J Pharmacol Exp Ther1997 Mar 01; 280
AB  - The role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in the initiation and propagation of limbic motor seizures in rats was examined by the intracerebral and systemic administration of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (f) quinoxaline (NBQX), a selective antagonist of the AMPA subtype of glutamate receptor. Limbic motor seizures were evoked focally by the application of the γ-aminobutyric acid receptor antagonist, bicuculline, into area tempestas, an epileptogenic site in the deep anterior piriform cortex. Before eliciting seizures, NBQX was applied focally into either 1) area tempestas or 2) perirhinal or posterior piriform cortex ipsilateral to the area tempestas from which seizures were evoked. In addition, pretreatment with i.p. NBQX was evaluated for anticonvulsant actions against area tempestas-evoked clonic or systemically evoked tonic seizures. In all conditions, a dose-dependent decrease in the severity of seizures was obtained with NBQX. With focal intracerebral administration, a dose of 500 pmol of NBQX consistently protected against limbic motor seizures, with partial protection achieved with 100 pmol. After i.p. administration, 2.5 and 5.0 mg/kg significantly protected the rats from both limbic motor seizures and tonic extensor seizures. No overt disturbance of spontaneous behavior was associated with the anticonvulsant doses of NBQX. Moreover, both forebrain substrates of limbic motor seizures and hindbrain substrates of tonic extensor seizures were highly susceptible to disruption by NBQX. The results indicate that AMPA subtype of glutamate receptors are crucial mediators of seizure propagation via perirhinal and piriform cortics. The American Society for Pharmacology and Experimental Therapeutics