Date of Award


Degree Type


Degree Name

Doctor of Philosophy


This thesis evaluated the hypothesis that N-methyl-D-aspartate (NMDA) receptor activity is essential for the development of kindling and/or the maintenance of the kindled state in male hooded rats. Kindling was produced by the infusion of carbachol, a muscarinic cholinergic agonist, directly into either the basolateral nucleus of the amygdala or the dentate gyrus of the hippocampus. The infusions of carbachol took place over 70 seconds and were given every 2 days. At a previously determined time before the infusion of carbachol, either APV (DL-aminophosphonovaleric acid, infused into the site of recording) or NPC 17742 (2R,4R,2S-(2-amino-4,5(cyclohexyl)-7-phosphonoheptanoic acid, i.p.) was given. Both APV and NPC 17742 are competitive NMDA antagonists and the interval between the administration of the NMDA antagonist and carbachol was previously found to be effective in maximally blocking NMDA receptor activity. The results indicated that seizure activity progressed in both sites, but that there was some retardation in the development of convulsions in the NMDA antagonist-treated rats as compared to their controls. There was no effect of APV or NPC on previously kindled seizures. As there was a limited effect of NPC 17742 on seizure activity and convulsions, a further study examining the effects of NPC 17742 on electrical kindling was undertaken. NPC 17742 retarded the development of seizure activity and convulsions, although it did not affect the expression of previously kindled seizures. Thus, NPC 17742 has an effect similar to other NMDA antagonists on electrical kindling. However, NPC 17742 did not completely retard the development of seizures, as all NPC-treated rats exhibited some form of convulsive activity. These results indicate that the blockade of NMDA receptor activity, through the preadministration of the NMDA antagonists, APV or NPC 17742, did not completely block kindling with carbachol, although they did retard the development of convulsions. As well, the blockade of NMDA receptor activity did not affect the expression of previously kindled seizures. Thus, NMDA-receptor activity is not essential for the development of kindling, although it may play a role in the development of seizures.



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