Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen.
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| 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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