Electrical kindling of the amygdala is a widely used animal model of epilepsy. Previous summaries of this project have documented the remarkable spatio-temporal evolution of the induction of the proto-oncogene c-fos with amygdala kindling. These findings were extended by the observation that c-fos mRNA was induced only on the contralateral side of the brain in a kindled rat that experienced a spontaneous seizure (i.e., required no electrical stimulation). This finding was rather surprising since: (A) c-fos was bilaterally induced in fully kindled rats upon seizure elicitation by electrical stimulation, and, (B) the only unilateral c-fos induction previously observed was on the stimulated side (ipsilateral) before the animals were fully kindled. This new finding of c-fos induction on the contralateral side in a fully kindled rat with a spontaneous seizure suggests transfer of the epileptogenic focus from the site of kindling stimulation to a different focus (not requiring electrical stimulation) on the contralateral side of the brain. Using receptor autoradiography, Dr. Clark observed changes in the serotonin (5-HT) receptor system in the dentate gyrus of the hippocampus in fully kindled rats. Kindling induced a persistent bilateral increase in 5-HT1A receptor binding (increased at 4 hr, 24 hr, and 4 days after the last stimulation). However, 5-HT1B receptor binding was increased only after 4 days. Binding to the 5-HT transporter was transiently decreased (only at the 4-hr time point) following amygdaloid kindled seizures. These 5-HT changes were observed only in the dentate gyrus and suggest that the hippocampal 5-HT system may be involved in kin- dled seizures. Drs. Clark and Smith studied the regulation of mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA in kindled rats by in situ hybridization. Both MR and GR mRNA were increased in the dentate gyrus 4 hr after the last kindled seizure. The MR mRNA remained elevated at 24 hr, whereas the expression of GR mRNA was significantly less than sham controls at 24 hr. However, both steroid receptor mRNAs returned to control values by 4 days. The data suggest that adrenal steroids may be important endogenous signals in brain during electrical kindling, and that MR and GR may be differentially regulated.
