EFFECT OF AMYGDALOID KINDLING ON THE HIGH-AFFINITY AND LOW-AFFINITY [H-3] TCP BINDING-SITES OF THE RAT CNS

The regulation of the binding sites of [H-3]TCP, a non-competitive ligand of the N-methyl-D-aspartate (NMDA) receptor, was studied on membranes prepared from different CNS regions of amygdaloid-kindled rats. The high-affinity binding sites (K(d)H = 4.2-7.4 nM), identified as the NMDA-gated ion channels, were not affected by kindling or by a daily injection of TCP (5 mg/kg before each electrical stimulation) which prevented kindling. These results suggest that the NMDA receptors participate to the establishment and not to the permanence of kindling. Kindling increases the number of low affinity [H-3]TCP binding sites in the hippocampus (+21%, P < 0.01) without change of the affinity (K(d)L = 340 nM). In the striatum both K(d)L and B(max)L were increased (3.3-4.4 fold, P <0.001) in animals pretreated with TCP before each electrical stimulation for 20 days. These last results argue in favour of a function of the low-affinity [H-3]TCP binding sites, the nature of which remains to be determined.