THE EFFECT OF DIZOCILPINE AND ENADOLINE ON IMMEDIATE-EARLY GENE-EXPRESSION IN THE GERBIL GLOBAL-ISCHEMIA MODEL

Increases in mRNA levels for c-fos, c-jun, junB, hsp70 and NGFI-A were observed in the dentate gyrus of the hippocampus following 7 min isch aemia in the Mongolian gerbil. The response was rapid and transient (3 0 min to 4 hr) for NGFI-A, jun B and c-fos mRNA. In contrast c-jun mRN A remained increased for several hours. Hsp70 increased in the dentate gyrus 1 hr after the insult, returned to control values at 4 hr and s howed a secondary increase at 24 hr. At 24 hr increased hsp 70 mRNA wa s observed in other regions of the CNS, i.e. CA1, CA2, CA3 and cortex. The non-competitive NMDA receptor antagonist, dizoclipine, attenuated the increases in IEG expression and was neuroprotective. In contrast the kappa opiate receptor agonist, enadoline, protected the CA1 neuron es from degeneration but did not inhibit the increased levels of IEG m RNA. Increases in hsp70 mRNA were reduced to baseline by both enadolin e and dizocilpine. These results suggest that inhibition of IEG expres sion is not a prerequisite for neuroprotection. However, hsp70 was pre dictive of neuronal protection and may be a useful assay in this and r elated models.