LONG-TERM EFFECTS OF EXCITATORY AMINO-ACID ANTAGONISTS NBQX AND MK-801 ON THE DEVELOPING BRAIN

Because of the critical role of excitatory amino acids (EAAs) in epile ptogenesis and seizure-induced brain damage, EAA antagonists are now b eing considered as a possible therapy for seizures. However, during de velopment EAAs play a pivotal role in learning, memory, and brain plas ticity. To evaluate the long-term effects of a short course of EAA ant agonists on the developing brain, a non-NMDA antagonist, NBQX, or a NM DA antagonist, MK-801, were administered over 7 days by osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10 day old rats. Alternatively, 10 and 20 day old rats received a 7 day cour se of intraperitoneal (i.p.) NBQX. one month later, the NBQX-, MK-801- treated rats, and controls underwent a series of behavioral studies: h andling test. open field, and Morris water maze. Flurothyl inhalation was used to test seizure susceptibility in all groups. Although all of the rats treated with NBQX via osmotic pumps had spontaneous seizures , rats surviving infusion of EAAs had no deficits in learning, memory, or behavior and did not differ from controls in seizure susceptibilit y with flurothyl. In the developing animal, a short-term course of EAA antagonists leads to no long-term adverse effects on behavior or seiz ure susceptibility.