NBQX PREVENTS CONTRALATERAL BUT NOT IPSILATERAL SEIZURE-INDUCED CYTOTOXICITY OF KAINATE BUT NOT AMPA-REVERSAL AT HIGH-DOSES OF NBQX

THE non-N-methyl-D-aspartate (NMDA) glutamate agonists are potent conv ulsants, and cause neuronal loss in many regions of the limbic system in the brain. Kainate or pha-amino-3-hydroxy-5-methyl-4-isoxazolepropi onate (AMPA) and the non-NMDA antagonist dihydroxy-6-nitro-7-sulphamoy l-benzo(F)quinoxaline (NBQX) were concomitantly injected unilaterally into the rat dorsal hippocampus. Kainate with low doses of NBQX (12.5- 25 nmol) almost completely prevented damage to the contralateral but n ot ipsilateral limbic areas (distal toxicity). In most animals, damage was still found in the contralateral midline thalamic nuclei. In cont rast, high doses of NBQX (95-190 nmol) gave no protection to either si de. AMPA showed a trend for a reduction in limbic damage to both sides with increasing dose of NBQX. At the highest doses, NBQX prevented da mage to both sides.