Inhibition of the development of electrical kindling of the prepyriform cortex by daily focal injections of excitatory amino acid antagonists.
The effects of daily focal injections of excitatory amino acid antagonists into the prepyriform cortex on the development of electrically kindled seizures at this site were studied. The selective 'NMDA receptor' antagonists 2-amino-7-phosphonoheptanoic acid (AP7) and 3-[+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) significantly inhibited the development of the electrically evoked afterdischarge over a 10 day period and prevented the development of the motor seizure responses. The 'kainate and quisqualate receptor' antagonist gamma-D-glutamylaminomethyl sulphonic acid (GAMS) showed less potent but still significant inhibitory actions on these responses. When drug treatment ceased, kindling progressed in all animals at a rate similar to that of the control (buffer-treated) animals. These results suggest a critical role for NMDA receptors in the primary neuronal events initiating the epileptiform activity in this animal model of epilepsy.
Croucher
M J
MJ
Department of Biochemistry, Imperial College of Science and Technology, London, U.K.
Bradford
H F
HF
Sunter
D C
DC
Watkins
J C
JC
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004594:Electrophysiology; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007267:Injections; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000927:Anticonvulsants; D010879:Piperazines; D005973:Glutamine; D015763:2-Amino-5-phosphonovalerate; C042626:gamma-glutamylaminomethylsulfonic acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C031231:2-amino-7-phosphonoheptanoic acid