ENHANCEMENT OF PAIRED-PULSE DEPRESSION IN THE DENTATE GYRUS IN-VIVO BY THE NMDA ANTAGONIST, MK-801, AND ELECTRICAL KINDLING

We have previously demonstrated that late paired-pulse depression of d entate granule cell field potentials decreases when stimulus intensity is increased from moderate to high levels. Voltage-dependent N-methyl -D-aspartate (NMDA) currents are increasingly activated within this st imulus range, and are enhanced following the development of kindled se izures. The NMDA antagonist, MK-801 (0.25 and 1.0 mg/kg, i.p.), was us ed in the present experiments to evaluate the contribution of NMDA cur rents to the loss of late paired-pulse depression at high stimulus int ensities in naive and kindled rats. Paired-pulse stimulus intensity fu nctions were obtained from animals prepared with chronic electrodes in the perforant path and dentate gyrus. MK-801 administration had no ef fect on the stimulus intensity function for early paired-pulse depress ion (20-30 ms interpulse intervals, IPI) in either preparation. Late p aired-pulse depression (150-500 ms IPI) was significantly enhanced in naive rats by MK-801. In contrast, MK-801 had no effect on the potenti ation of late paired-pulse depression recorded from kindled animals. T hese findings suggest that the ability of NMDA currents to reduce the strength of late paired-pulse depression in naive animals is altered f ollowing the development of kindled seizures. A decrease in late paire d-pulse depression was observed at high stimulus intensities under all experimental conditions. The latter findings indicate that the proces ses responsible for the reduction in late paired-pulse depression at h igh stimulus intensities are unaffected by either NMDA or kindling-ind uced modulation of late paired-pulse depression.