Regional changes in c-fos mRNA in rat brain after i.v. or i.c.v. NMDA injections.

These studies were undertaken to determine if convulsant doses of i.c.v. vs i.v. administered NMDA exhibit differential specificity for anatomical regions of the brain in stimulating c-fos. In rats i.c.v. or i.v. NMDA produced behaviorally similar clonic (popcorn) convulsions associated with transient increases in c-fos mRNA in different brain areas. Transcription of c-fos mRNA peaked at 30 min post-treatment regardless of the route of administration. However, the route of administration clearly influenced the anatomical specificity of the NMDA-induced c-fos mRNA changes. For example, following i.c.v. administration maximal stimulation in c-fos mRNA was measured in the cerebellum. In contrast, i.v. NMDA produced maximal c-fos mRNA stimulation in the cerebral cortex. Our results demonstrate that NMDA has differential anatomical specificity for molecular signaling in rat brain and suggest that the route of NMDA administration may influence its pathophysiological response.