Evidence for a role of glycine in area tempestas for triggering convulsive seizures.
An epileptogenic region of the deep prepiriform cortex, area tempestas (AT), triggers convulsive seizures in response to the focal application of GABA antagonists, muscarinic agonists and excitatory amino acid agonists. In all cases, activation of N-methyl-D-aspartate (NMDA)-sensitive receptors in AT is required for triggering convulsions from this site. To determine whether glycine is involved in the activation of NMDA-sensitive receptors in AT, we evaluated the effects of 7-chlorokynurenic acid (7-CLKYN); kynurenic acid (KYN) and 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on convulsions evoked by focal application of bicuculline methiodide (118 pmol) into AT. Significant anticonvulsant effects were obtained with 1.25 nmol of 7-CLKYN, 6.25 nmol of KYN and 60 nmol of HA-966 in AT. 7-CLKYN in AT also blocked the convulsant effects of carbachol (273 pmol) and kainic acid (117 pmol) injected into AT. When injected into the lateral ventricle, high doses (50-100 nmol) of 7-CLKYN were required in order to attenuate AT-evoked convulsions and these doses produced marked ataxia. In contrast, no ataxia was observed following 7-CLKYN application into AT at anticonvulsant doses. Our results implicate glycine antagonism as a mechanism for preventing convulsions triggered via NMDA receptor activation in AT and demonstrate that a different anatomical site of action is responsible for the motor impairment produced by glycine antagonism.
Wardas
J
J
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
Graham
J
J
Gale
K
K
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000503:physiopathology*; D005998:Glycine / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*
D000927:Anticonvulsants; D011760:Pyrrolidinones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D002217:Carbachol; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D007608:Kainic Acid; D005998:Glycine; D001640:Bicuculline