AMPA/kainate-related mechanisms contribute to convulsant and proconvulsanteffects of 3-nitropropionic acid

The role of the glutamatergic system in the convulsant and proconvulsant ac tion of a mitochondrial toxin, 3-nitropropionic acid, was studied in mice. The occurrence of 3-nitropropionic acid-induced seizures was inhibited by t he alpha-amino-2,3-dihydro-5-methyl-3-oxo-isoxazole-propionate (AMPA)/kaina te receptor antagonists, 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione disodium (NBQX) and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-be nzodiazepine HCl (GYKI 52466), with ED50 of 14.1 (7.9-25.2) and 7.2 (5.3-9. 6) mg/kg, respectively. The N-methyl-D-aspartate (NMDA) receptor antagonist s, dizocilpine (MK-801) and 3-(2-carboxypiperazine-4-yl)propenyl-1-phosphon ic acid (CPPene), were ineffective. Moreover, 3-nitropropionic acid given i n a subthreshold dose potently enhanced seizures generated by intracerebrov entricular administration of AMPA and kainate, lowering their CD50 from 0.9 8 (0.83-1.17) and 0.73 (0.64-0.83) to 0.55 (0.45-0.66) (P < 0.001) and 0.58 (0.51-0.65) (P < 0.05) nmol, respectively. In contrast, NMDA action was no t changed by 3-nitropropionic acid application. We conclude that AMPA/kaina te-mediated events are involved in proconvulsive and convulsive effects of 3-nitropropionic acid. (C) 1999 Elsevier Science B.V. All rights reserved.