MK801 pretreatment reduces kainic acid-induced spontaneous seizures in prepubescent rats

MK801 is a noncompetitive blocker of N-methyl-d-aspartate receptors which has antiepileptic properties. To evaluate whether MK801 pretreatment in immature rats affects the future spontaneous recurrent seizure (SRS) rate or seizure susceptibility in a model of limbic epilepsy, MK801 (0.2 or 1.0 mg/kg, i.p.) or saline was administered to prepubescent rats 30 min prior to kainic acid (KA; 10 mg/kg, i.p.). With or without MK801 pretreatment, KA caused prolonged status epilepticus. SRS rate over the next 4 weeks, as assessed by intermittent video monitoring, was significantly lower in MK801 treated rats than in those which received KA alone. In addition, fewer MK801 treated rats (43%) developed SRS than those which got KA alone (88%). Susceptibility to generalized seizures was then tested using the volatile convulsant flurothyl; at both doses of MK801, flurothyl seizure latency was significantly greater in pretreated animals. These results show that MK801 pretreatment prior to KA induced status epilepticus reduces subsequent SRS frequency and flurothyl seizure susceptibility, while not substantially altering the acute epileptogenic effects of KA.