EXPRESSION OF C-FOS PROTEIN IN THE EXPERIMENTAL EPILEPSY INDUCED BY PILOCARPINE

The expression of the c-fos proto-oncogene, as estimated by immunohist ochemistry of the FOS nuclear protein, was studied in both focal and g eneralized seizures induced in rats by systemic administration of pilo carpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconv ulsant dose of pilocarpine (200 mg/kg) or the association of a convuls ant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 do pamine receptor antagonist. This seizure pattern resulted in FOS accum ulation in certain limbic areas, namely, the piriform cortex, amygdala , and olfactory tubercle. On the other hand, in rats developing genera lized seizures, accumulation of FOS was also found in hippocampus, cin gulate cortex, frontal cortex, striatum, accumbens, as well as in cert ain thalamic nuclei. Generalized seizures, including motor limbic seiz ures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of be havioural alterations induced by pilocarpine and the proto-oncogene ac tivation. The results provide the basis for mapping the areas of origi n and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system.