Biochemical evidence for enhanced sensitivity to N-methyl-D-aspartate in the hippocampal formation of kindled rats.

The inhibitory effect of N-methyl-D-aspartate (NMDA) upon carbachol-stimulated phosphoinositide (PI) hydrolysis was studied in transverse hippocampal slices prepared from control and amygdaloid kindled rats. Kindling significantly increased the inhibitory effect of NMDA (10 microM) in slices prepared from animals 24 h after the last class 5 kindled seizure, resulting in a steepening of the dose-response curve for NMDA. The enhanced sensitivity to NMDA was long-lasting in that it was also present in slices prepared from animals sacrificed 28-35 days after the last class 5 seizure. The increased sensitivity to NMDA was selective in that inhibition of carbachol-stimulated PI hydrolysis by kainic acid or phorbol-12,13-diacetate was not different in control and kindled animals. Neither NMDA, kainic acid, phorbol ester nor carbachol alone had any significantly different effects in slices from kindled versus control animals. These data demonstrate a selective and enhanced sensitivity of the kindled hippocampus to NMDA. This enhanced sensitivity to the principal class of excitatory neurotransmitter may be one mechanism underlying the development and maintenance of kindled epilepsy.