REGIONAL INDUCTION OF C-FOS MESSENGER-RNA BY NMDA - A QUANTITATIVE INSITU HYBRIDIZATION STUDY

THE regional expression of c-fos mRNA following acute NMDA administration has been mapped by quantitative in-situ hybridization using S-35-c-fos DNA probe. NMDA-induced expression of c-fos mRNA is discrete, largely restricted to the dentate gyrus of the hippocampus and piriform cortex. This distribution is different from the much more widespread distribution of NMDA receptors detected by ligand autoradiography. Expression of c-fos mRNA induced by 225 mg kg-1 NMDA was stereospecifically blocked by pretreatment with the NMDA receptor/ionophore complex blocker, MK-801. Large doses of NMDA (> 175 mg kg-1) were needed for increased expression of c-fos mRNA. Animals which had seizures after acute NMDA administration always had high levels of c-fos mRNA, but equally high levels of c-fos mRNA expression were found in some seizure-free animals. Thus overt seizure activity may not be necessary for c-fos mRNA expression.