Expression of c-fos mRNA in rat brain after intracerebroventricular administration of corticotropin-releasing hormone.

Expression of the proto-oncogene c-fos is known to increase in rat brain following various types of seizures. Measuring c-fos mRNA or protein levels was shown to be a good cellular marker for neurons activated during central nervous system (CNS) excitation. In this study, we used in situ hybridization analysis of c-fos mRNA to determine brain regions activated by a peptide that has been closely linked to stress responsivity and kindling-like seizure activity. Corticotropin-releasing hormone (CRH) was injected into the left lateral ventricle of rats and produced the late onset of seizures between 1.5-5 h after its administration. Rats were sacrificed at various time points after the administration of CRH or sterile water, and c-fos mRNA levels were determined. In the preseizure state, CRH increased c-fos unilaterally in several cerebral cortical structures (most prominently in the dorsal endopiriform nucleus and in the piriform and insular cortices). CRH-induced seizures increased c-fos bilaterally in the same cortical regions, and in addition, in the hippocampus and olfactory bulb. The data are congruous with the hypothesis that intracerebroventricularly (i.c.v.) administered CRH elicits a rapid kindling-like response.