The N-methyl-D-aspartate antagonists aminophosphonovalerate and carboxypiperazinephosphonate retard the development and expression of kindled seizures.
To investigate the possible role of N-methyl-D-aspartate (NMDA) receptors in the development and expression of amygdaloid-kindled seizures, rats were either chronically infused with 2-amino-5-phosphonovalerate (APV, 20-40 mM) or pre-injected with carboxypiperazine-phosphonate (CPP, 1-10 mg/kg), both selective NMDA-receptor antagonists, and then kindled from the amygdala. At the higher dose (40 mM), APV blocked the induction of long-term potentiation in the dentate gyrus. APV also retarded clinical seizure development dose-dependently and increased seizure thresholds without affecting afterdischarge (AD) duration. These same doses of APV had only small anticonvulsant effects on established kindled seizures. Although CPP (1-10 mg/kg) had no effect when rats were kindled 45 min after injection it dose-dependently retarded focal and generalization stages at the 150 min injection-kindling interval. Once relieved of drug, animals proceeded to develop stage 5 seizures with shorter duration ADs than saline-control animals. When the previously-kindled, saline groups were crossed to CPP a small depressant effect on seizure expression was observed. These results suggest that NMDA receptors are primarily involved in kindling development rather than in maintaining the kindled state.
Holmes
K H
KH
Department of Psychology, University of Otago, Dunedin, New Zealand.
Bilkey
D K
DK
Laverty
R
R
Goddard
G V
GV
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid