Electrophysiological evidence for activation of NMDA receptors and its antagonism by MK-801 in cerebral ischemia.

We studied the effects of iontophoretically administered MK-801 (50-150 nA) on ischemic changes on the CA1 hippocampal field potential. Twenty rats under urethane anesthesia, of which the hippocampal field response was depressed or lost upon ligation of the carotid arteries, were used. MK-801 applications starting before carotid ligation, decreased the depression of the field response in 8 of 11 trials. MK-801 was applied after the appearance of ischemic changes and partly restored the deteriorated hippocampal field potential in 16 of 34 penetrations. MK-801 was ineffective in preventing or restoring the severely depressed or lost evoked activity. During ischemia a DC potential shift of -32.6 +/- 3.7 mV (n = 10) was recorded. MK-801 reduced the amplitude of the DC potential shift by 50% when applied before (n = 6) or after (n = 4) the initiation of ischemia. Activation of N-methyl-D-aspartate (NMDA) receptors by glutamate or N-methyl-DL-aspartate (NMDLA) induces a slow negative wave on the field response. During ischemia a similar negative wave spontaneously appeared in 9 trials and was also induced with low currents (5-10 nA) of NMDLA which were insufficient to evoke the NMDA-mediated wave before ischemia. These data provide electrophysiological evidence that NMDA receptors are activated during ischemia and MK-801 reduces ischemia neuronal dysfunction.