Selective stimulation of kainate but not quisqualate or NMDA receptors in substantia nigra evokes limbic motor seizures.
Bilateral microinjection of kainic acid (30-117 pmol) into the substantia nigra induced convulsive seizures resembling those elicited from limbic system structures. The convulsive seizures, which consisted of facial and forelimb clonus with rearing and falling, developed after a latency of more than 30 min and were preceded by wet dog shakes and non-convulsive seizure activity registered electroencephalographically. The convulsant effect of intranigral kainic acid was strictly dose-dependent (ED50 = 60 pmol) and anatomically site-specific. Stimulation of nigral neurons by focal application of agonists for NMDA or quisqualate receptors, or by focal application of the GABA antagonist, bicuculline, was without convulsant effects. The convulsant action of intranigral kainic acid was prevented by the focal application of kynurenic acid (100 nmol) but not by 2-amino-7-phosphonoheptanoic acid (AP-7) (25 nmol) or 7-chlorokynurenic acid (20 nmol), suggesting that the convulsant effect of kainic acid in the substantia nigra does not depend upon activation of NMDA receptors in this region.
Maggio
R
R
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
Liminga
U
U
Gale
K
K
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants; D004569:Electroencephalography / Q000187:drug effects; D007267:Injections; D007608:Kainic Acid / Q000494:pharmacology*; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
D001640:Bicuculline; D003292:Convulsants; D007608:Kainic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter