STATUS EPILEPTICUS CAUSES LONG-TERM NMDA RECEPTOR-DEPENDENT BEHAVIORAL-CHANGES AND COGNITIVE DEFICITS

Purpose: The role of N-methyl-D-aspartate (NMDA)-receptor activation o n behavioral and cognitive changes after status epilepticus (SE) is un known. In this study, behavioral and cognitive changes after SE were e valuated in the short and long term and in rats in which the NMDA rece ptor was inactivated during SE. Methods: Pilocarpine (350 mg/kg) was i njected to induce SE. Inhibition of the NMDA receptor during SE was ac hieved with MK-801 (4 mg/kg). Seizure intensity during SE was monitore d by electroencephalography (EEG). After SE, behavioral studies were p erformed to identify abnormal behavior by using behavioral tests adapt ed from Moser's functional observational battery. Cognitive changes we re assessed by using the Morris Water Maze (MWM). Results: Pilocarpine -treated animals scored significantly higher on two of the behavioral tests: the Touch test and the Pick-Up test. These behavioral changes o ccurred very soon after SE, with the earliest changes observed 2 days after SE and persisting for the life of the animal. Inhibition of the NMDA receptor with MK-801 completely inhibited these behavioral change s under conditions that did not alter the duration of SE. In addition, pilocarpine-treated animals exhibited cognitive deficits as determine d by using the MWM. Six weeks after SE, the animals displayed signific antly longer latencies to locate the hidden platform on this test. The impaired performance on the MWM also occurred as early as 5 days afte r SE. These cognitive deficits were prevented in animals treated with MK-801 during SE. Conclusions: The results indicate that behavioral an d cognitive changes occur soon after SE, are permanent, and are depend ent on NMDA-receptor activation during SE. NMDA-receptor activation ma y play an important role in causing cognitive and behavioral morbidity after recovery from SE.