The effects of N-methyl-D-aspartate (NMDA) and its competitive antagonist, 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), injected into caudate-putamen on kindled amygdaloid seizures in rats.

N-methyl-D-aspartate (NMDA) is an agonist of NMDA receptors and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) is an NMDA receptor antagonist. NMDA (1 or 2 nmol per side) or CPP (2.5 or 10 nmol per side) was injected into the bilateral caudate-putamen of amygdaloid-kindled rats. In addition, CPP (10 nmol) was ipsilaterally or contralaterally injected into the unilateral caudate-putamen. Either 20 min after NMDA or 60 min after CPP, the kindled amygdala was stimulated at the generalized seizure triggering threshold. In a few animals tested, injection of NMDA into the bilateral caudate-putamen produced transient spiking activity, with no clinical manifestations. This feature began about 5 min after the injection and lasted about 10 s. When these animals were excluded from the statistical analysis, NMDA in the caudate-putamen showed a weak and non-significant anticonvulsant action. Injection of CPP into the bilateral caudate-putamen caused no ictal change, but markedly suppressed the kindled seizures. Injection of CPP into the unilateral caudate-putamen, regardless of the site, did not cause any ictal change, or affect the stimulation of the amygdala. These findings suggest that: (1) NMDA receptors in the caudate-putamen facilitate the development of kindled amygdaloid seizures; (2) activation of NMDA receptors in the bilateral, but not in the unilateral, caudate-putamen is required for the generalization and expression of kindled amygdaloid seizures.