Role of the N-methyl-D-aspartate-type receptors in the development and maintenance of hippocampal kindling in rats.
The effect of intrahippocampal infusion of 70 nmol (1 microliter/2 min) D,L-2-amino-7-phosphonoheptanoic acid (APH), a selective antagonist of N-methyl-D-aspartate (NMDA)-type receptors, was studied on behavioral seizures and afterdischarge (AD) at different stages of hippocampal kindling in rats. After completion of kindling (3 consecutive stage 5 seizures) APH infusion at the site of stimulation (granule cells of dentate gyrus) 60 min before stimulus delivery (50 Hz, 2 ms monophasic rectangular wave pulses for 1 s, current intensity 60-200 microA) suppressed the behavioral convulsions and focal AD. Four stimulations were needed after drug injection to recover stage 5 seizures and AD. When similarly injected early in kindling (stage 1-2) APH had no effect on the AD duration but significantly increased (by 37% with respect to controls) the number of stimulations needed to reach the first stage 5 seizures. Thus, it appears that NMDA-type receptors at the site of stimulation become progressively involved during the development of kindling and mediate the behavioral convulsions and focal AD observed at stage 5.
Vezzani
A
A
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Wu
H Q
HQ
Moneta
E
E
Samanin
R
R
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid