Abstract |
We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold. N-Methyl-D-aspartate (N-Me-D-Asp) is an excitatory amino acid derivative that is a powerful convulsant agent when injected into the cerebral cortex, amygdala, or hippocampus in rats. Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizures induced by pilocarpine (injected systemically), with an ED50 of 0.7 nmol (range 0.5-1.0 nmol). Lesioning the caudate-putamen (by bilateral microinjection of the excitotoxin ibotenate) converted subconvulsant doses of pilocarpine into convulsant ones. The anticonvulsant action of N-Me-D-Asp in the caudate-putamen was reversed by blocking gamma-aminobutyrate-mediated inhibition in the substantia nigra pars reticulata or in the entopeduncular nucleus. The results suggest that the caudate-putamen and its gamma-aminobutyrate-dependent efferent pathways modulate the threshold for seizures in the limbic forebrain.
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Authors | L Turski, B S Meldrum, E A Cavalheiro, L S Calderazzo-Filho, Z A Bortolotto, C Ikonomidou-Turski, W A Turski |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 84
Issue 6
Pg. 1689-93
(Mar 1987)
ISSN: 0027-8424 [Print] United States |
PMID | 3550795
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- Pilocarpine
- Ibotenic Acid
- Aspartic Acid
- N-Methylaspartate
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Topics |
- Animals
- Anticonvulsants
(pharmacology)
- Aspartic Acid
(analogs & derivatives, pharmacology)
- Caudate Nucleus
(drug effects)
- Epilepsy
(etiology)
- Ibotenic Acid
(pharmacology)
- Male
- N-Methylaspartate
- Pilocarpine
(pharmacology)
- Putamen
(drug effects)
- Rats
- Rats, Inbred Strains
- Substantia Nigra
(drug effects)
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