Consequences of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blockade during status epilepticus in the developing brain

Abstract

To investigate if AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activation contributes to acute manifestations and long term consequences of status epilepticus (SE), we administered the AMPA receptor antagonist NBQX to P35 rats undergoing kainic acid (KA)-induced SE. NBQX (30 mg/kg/dose) given intraperitoneally (i.p.) at 30, 60 and 90 min after i.p. KA injection (12 mg/kg) reduced severity of SE. When tested as adults, rats that had received KA and NBQX were similar to controls with no long term impairment in visuospatial memory (assessed by the water maze test), or histologic damage in the CA1 or CA3 hippocampal subfields. However, both P35 groups, those receiving KA alone and those receiving KA and NBQX, had similar rates of spontaneous recurrent seizures (SRS). In P15 rats, NBQX resulted in increased acute mortality from KA associated SE. These results indicate that the effects of NBQX on KA-induced SE are age dependent, and that non-NMDA receptor activation contributes to the acute manifestations and to the long term sequelae seen after KA-induced SE in the prepubescent rat brain.