Synergy between diazepam and NBQX in preventing neuronal death caused by non-NMDA agonists

The non-N-methyl-D-aspartate (NMDA) glutamate receptor agonists kainate and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), when injected into the rat dorsal hippocampus, cause neuronal death directly by activating non-NMDA receptors and as a consequence of initiating seizure activity. Co-injection of the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 12.5-95 nmol) was partially effective in preventing up to about 60% of the direct excitotoxicity. On the other hand, diazepam (6 x 5 mg kg-1, i.p.) had only a minor protective effect against the direct neuronal damage, but was effective in preventing almost all the extra-hippocampal loss of neurones caused by seizure activity. The combination of intracerebral NBQX and systemic 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.