Abstracts

RATIONALE: Seizure susceptibility appears to be related to enhanced glutamatergic excitatory synaptic transmission with alterations in the expression of ionotropic glutamate receptors. We wondered if AMPA and NMDA receptor subunit levels are changed following epileptogenesis induced by amygdalar FeCl3 injection. METHODS: We used western blots to measure levels of these subunits in the ipsilateral and contralateral hippocampus at various times after FeCl3 injection into the amygdaloid body. RESULTS: With acute seizures, at +5 days after injection of FeCl3, levels of Glu-R1, NMDA-R1, and NMDA-R2 were markedly increased in both hippocampal regions, with quantities at least 2-3 times baseline. By +15 and +30 days after injection, when chronic, spontaneous limbic seizures were occurring, the levels of Glu-R2 and Glu-R3 were increased, and levels of Glu-R1 and NMDA-R1 and R2 were decreased when compared with the quantities at +5 days. CONCLUSIONS: Increase in the levels of NMDA-R1 & R2 at +5 days is consistent with the occurrence of up-regulation of NMDA receptor production in the early stages of epileptogenesis. However, Glu-R2 suppresses glutamate receptor-mediated Ca++ influx. Increased expression of Glu-R2 with development of chronic recurrent seizures may be a compensatory effect during epileptogenesis, with resultant neural responses to propagated seizures.