DIFFERENTIAL TEMPORAL PATTERNS OF EXPRESSION OF IMMEDIATE-EARLY GENESIN CEREBRAL-CORTEX INDUCED BY INTRACEREBRAL EXCITOTOXIN INJECTION - SENSITIVITY TO DEXAMETHASONE AND MK-801

A number of conditions associated with persistent excitation such as e lectrically and chemically-induced seizures cause a rapid increase in the expression of immediate early genes (IEG) such as c-fos. In this s tudy the time-course of induction of c-jun, jun-B and zif ?268 mRNA by kainate was characterized in rat cerebral cortex and compared to that of c-fos mRNA induction. Unilateral injection of kainate. into the nu cleus basalis caused a significant induction of c-jun mRNA in cerebral cortex from 4 hr which was maximal at 8 hr, being 3 times greater in ipsilateral cortex than in control cortex. This pattern was also shown for jun-B and was similar, but of small magnitude, to that obtained w ith c-fos mRNA, with a maximal increase at 8 hr, whilst the maximal in duction of zif-268 mRNA preceded these responses occurring at 4 hr. A marked difference was seen in duration in the c-jun induction which wa s maintained at a high level for at least 24 hr. Treatment of animals with MK-801 (within 30 min of injection of kainate) or dexamethasone ( 2-30 mg/kg) at the time of kainate injection significantly attenuated the response. The induction of c-fos mRNA by kainate injection was mos t sensitive to dexamethasone (2 mg/kg), whereas a higher dose (30 mg/k g) was required to attenuate the induction of zif-268 mRNA. These resu lts show that a time-dependent and co-ordinated induction of c-fos, c- jun, jun-B and zif-268 mRNA in cerebral cortex occurs in response to t he persistent excitation caused by excitotoxin injection which is medi ated by glutamate and shows a differential sensitivity to dexamethason e.