Gj. Lees et W. Leong, SYNERGY BETWEEN DIAZEPAM AND NBQX IN PREVENTING NEURONAL DEATH CAUSEDBY NON-NMDA AGONISTS, NeuroReport, 5(16), 1994, pp. 2149-2152
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.