Self-sustaining status epilepticus: A condition maintained by potentiationof glutamate receptors and by plastic changes in substance P and other peptide neuromodulators

We describe a model of self-sustaining status epilepticus (SSSE) induced by stimulation of the perforant path in free-running rats. In this model, sei zures can be transiently suppressed by intrahippocampal injection of a bloc ker of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate syn apses but return in the absence of further stimulation when the drug ceases to act. However, seizures are irreversibly abolished by blockers of N-meth yl-D-aspartate receptors given locally or systemically. SSSE is enhanced by substance P and its agonists and blocked by its antagonists. SSSE induces novel expression of substance P-like immunoreactivity in hippocampal princi pal cells. These changes and those in other limbic peptides may contribute to the maintenance of SSSE and to the modulation of hippocampal excitabilit y during epileptic seizures.