Antisense oligonucleotides to C-fos reduce postictal seizure susceptibility following fully kindled seizures in rats

In a previous study we demonstrated that increased FOS expression in the am ygdala induced by partial kindling seizures could be attenuated by administ ering c-Fos specific antisense oligonucleotides. In addition, we found that the administration of c-Fos antisense oligonucleotides at the beginning of the amygdala kindling process facilitated the appearance of stage V kindle d seizures. In the present study, we evaluated the effect of the suppressio n of FOS on the expression and severity of the generalized fully kindled se izures as well as on the susceptibility to additional ictal events during t he postictal and interictal periods. We observed that the administration of c-Fos antisense oligonucleotides did not modify the behavioral and electro graphic manifestations of generalized stage V kindled seizures. However, c- Fos antisense oligonucleotides significantly reduced the susceptibility to additional ictal events during the postictal refractory period. Hence, the increased FOS protein induced by generalized tonic clonic seizures may part icipate in postictal mechanisms. (C) 1999 Elsevier Science Ireland Ltd. Ail rights reserved.