Effects of amygdaloid kindling on NMDA receptor function and regulation

These studies were conducted to determine whether amygdaloid kindling results in the long-term alteration of NMDA receptors which could explain the persistent reduction in seizure threshold seen in this phenomenon. NMDA-induced [³H]norepinephrine (NE) release, NMDA-sensitive l-[³H]glutamate binding, and NMDA and glycine-enhanced [³H]TCP binding were measured in brain tissue from kindled rats and nonstimulated control rats 3 to 6 weeks after the last seizure. There was no difference in the ability of NMDA to induce [³H]NE release from kindled or control slices of amygdala or hippocampus. There was also no difference in the ability of phencyclidine (PCP) or Mg²⁺ to inhibit [³H]NE release induced by 100 μM NMDA. Equilibrium saturation experiments of NMDA-sensitive l-[³H]glutamate binding revealed no differences in K_D or B_max values between control and kindled cortex, amygdala, and hippocampus. The K_i values for NMDA displacement of l-[³H]glutamate binding also did not differ in kindled tissue. NMDA-enhanced [³H]TCP binding was similar in cortex, amygdala, and hippocampus of kindled and control tissues. Finally, glycine-enhanced [³H]TCP binding was not different in control or kindled tissues. These studies suggest that the NMDA recognition site and the modulation of the NMDA receptor/ion channel complex by magnesium, PCP, and glycine are not altered several weeks after the last seizure. Even though NMDA-mediated electrophysiological responses are reportedly enhanced in kindled tissue at that time, the mechanism(s) underlying the enhancement remains to be determined.