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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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.[1]


  1. Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen. Turski, L., Meldrum, B.S., Cavalheiro, E.A., Calderazzo-Filho, L.S., Bortolotto, Z.A., Ikonomidou-Turski, C., Turski, W.A. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
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