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.