SYNERGY BETWEEN DIAZEPAM AND NBQX IN PREVENTING NEURONAL DEATH CAUSEDBY NON-NMDA AGONISTS

THE non-N-methyl-D-aspartate (NMDA) glutamate receptor agonists kainat e and pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), when injected into the rat dorsal hippocampus, cause neuronal death directl y by activating non-NMDA receptors and as a consequence of initiating seizure activity. Co-injection of the non-NMDA antagonist dihydroxy-6- nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 12.5-95 nmol) was partia lly effective in preventing up to about 60% of the direct excitotoxici ty. On the other hand, diazepam (6 x 5 mg kg(-1), i.p.) had only a min or protective effect against the direct neuronal damage, but was effec tive in preventing almost all the extra-hippocampal loss of neurones c aused by seizure activity. The combination of intracerebral NBQX and s ystemic diazepam reduced the toxicity of kainate or AMPA to a greater extent than that found in the presence of either protectant alone. At optimum doses the neuronal cytotoxicity caused by non-NMDA agonists in the hippocampus was completely prevented.