The pathogenic role of the NMDA receptor in hyperthermia-induced seizures in developing rats

Hyperthermia-induced seizures (HS) in rats have been used as a model of febrile seizures. Activation of the N-methyl-D-aspartate (NMDA) receptor by increased extracellular glutamate (Glu) in the cortex during hyperthermia may be involved in the induction of HS and HS kindling. To confirm this hypothesis, the effects of a potent blocker of the NMDA receptor, MK-801, on the threshold and pattern of HS were evaluated. The threshold temperatures for rats given 0.1 (low dose) and 0.5 (high dose) mg/kg MK-801 (i.p.) for the first time were 41.6 degrees C (39.7-42) (median, range) and 42.0 (41.2-42.0), respectively, which were significantly higher than the 40.5 (39.4-41.2) for rats without MK-801 administration (P < 0.01). The recurrent occurrence of HS suppressed the increase in the threshold temperature with age, and changed the seizure from partial to generalized seizures (HS kindling), whereas these effects of recurrent HS on the threshold and pattern of HS were inhibited by the high dose (0.5 mg/kg) of MK-801. MK-801 blocks HS and HS kindling. The activation of the NMDA receptor during hyperthermia plays an important role in the induction of HS and HS kindling.