AGE-RELATED AND DOSE-RELATED NMDA INDUCTION OF FOS-LIKE IMMUNOREACTIVITY AND C-FOS MESSENGER-RNA IN THE ARCUATE NUCLEUS OF IMMATURE FEMALE RATS

Glutamate and the N-methyl-D-aspartate (NMDA) receptor are important regulatory components of the hypothalamic control of luteinizing hormone (LH) secretion. Peripheral injection of prepubertal rats with NMDA induces maximal secretion of LH within 8 min as well as the expression of the proto-oncogene, c-fos, within the mediobasal hypothalamus (MBH). Because the induction of the c-fos gene is recognized as a sensitive marker of neuronal activity, the detection and characterization of c-fos mRNA and Fos protein may be particularly useful in the analysis of the GnRH (gonadotropin releasing hormone) neuronal system. This study has examined the effect of different doses of NMDA on c-fos mRNA and Fos-like immunoreactivity (Fos-lir); the time-course of induction of c-fos mRNA and the appearance of Fos-lir expression and the ontogeny of NMDA-induced Fos-lir. Our results indicate that NMDA-induced c-fos mRNA and protein are maximal by 60 and 120 min, respectively. Both c-fos mRNA and protein attain peak levels using NMDA doses between 20 and 40 mg/kg. Ontological studies demonstrated that Fos-lir could be detected at 5 days after birth, but declined after sexual maturation. The data presented here indicate that the immunohistochemical localization of c-fos gene expression, in conjunction with in situ hybridization, is a useful technique for mapping NMDA-sensitive pathways and may provide anatomical and physiological evidence that better defines the glutamatergic control of sexual maturation.