N-G-NITRO-L-ARGININE DIFFERENTIALLY AFFECTS GLUTAMATE-INDUCED OR KAINATE-INDUCED SEIZURES

THE effects of nitric oxide (NO) synthase inhibitor, N-G-nitro-L-argin ine (NNA) on seizures induced by excitatory amino acids, bicuculline, pentylenetetrazol and pilocarpine were studied in mice. NNA (10 and 40 mg kg(-1), i.p.) enhanced the susceptibility to intracerebroventricul ar (i.c.v.) kainate (KA) which was reflected by a decrease in its conv ulsant dose 50% (CD50) from 0.66 nmol to 0.38 and 0.29 nmol/mouse, res pectively. Also, NNA (40 mg kg(-1)) increased the KA-induced mortality . Conversely, NNA (40 mg kg(-1)) produced an anticonvulsant effect aga inst i.c.v. glutamate whose CD50 value was significantly elevated from 0.49 mu mol to 0.84 mu mol/mouse. The convulsive activity of i.c.v. N -methyl-D-aspartic acid (NDMA), lpha-amino-3-hydroxy-5-methylisoxazole -4-propionic acid (AMPA), and trans-(+/-)-1-amino-1,3-cyclopentanedica rboxylic acid (trans-ACPD) was not affected by the pretreatment with N NA (40 mg kg(-1)). NNA (5-40 mg kg(-1)) also potentiated the convulsiv e action of systematic KA and KA-induced mortality but (up to 40 mg ka (-1)) remained without effect on seizures produced by bicuculline, N-m ethyl-D, L-aspartic acid (NMDLA), pentylenetetrazol, pilocarpine. Only bicuculline-produced lethality was significantly enhanced. It may be concluded that the manipulation of the NO level affects differently se izures arising from a diffuse stimulation of glutamate receptors and s eizures resulting from an activation of an individual subtype of these receptors. It is noteworthy that in the majority of convulsive tests used in this study, NNA exerted no modulatory effect.