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.