Intrahippocampal NMDA Administration Alters Fos, Fos-Related Antigens, and Opioid Peptide Immunoreactivity and mRNA in Rats.

In this study, the glutamate receptor agonist, NMDA, was used to induce epileptic seizures in order to compare the expression of the immediate early gene (IEG) products, Fos and Fos-related antigens (Fras), with the opioid peptides, dynorphin (DYN) and leu(5)-enkephalin (LE), in the rat hippocampus. Fos-ir and Fra-ir were observed in the dentate granule cells and nonpyramidal cells within the hippocampal formation at 1 h, and in all hippocampal cells and fields, 3 h following injection of NMDA into the ventral hippocampus. A detailed time-course analysis revealed a differential expression of Fos-ir and Fra-ir. In adjacent sections, a substantial decrease in DYN-ir and LE-ir in the mossy fibers occurred 1, 3, and 6 h after NMDA which was followed by a normalization or an elevation of the opioid peptides at later time points. Quantitative in situ hybridization histochemistry revealed that the hybridization signal representing c-fos mRNA was induced rapidly and transiently in hippocampal neurons. An increase in preproenkephalin (PPE) mRNA in the dentate granule cells was observed 1, 3, and 6 h after NMDA, with a peak at 6 h. Twenty-four and 48 h after NMDA, hybridization signals for PPE and preprodynorphin (PPD) were barely detectable. At 72 h, the level of PPD mRNA was not significantly different from control values. There is a different time course of expression for the Fos and Fra family of genes after in vivo NMDA. The significance of the results is discussed with regard to IEG regulation of opioid peptide gene expression.