Effect of MK-801 on dopamine release evoked by hypoxia combined with hypoglycemia.

[3H]dopamine ([3H]DA) release was measured from rat striatal slices under normoxic and hypoxic conditions. In some experiments hypoxia was combined with glucose withdrawal. Hypoxia increased the evoked release of dopamine without affecting resting release. Hypoglycemia itself increased only the resting release of [3H]DA. In the absence of glucose hypoxia provoked a dramatic rise in both resting and stimulation-evoked release of dopamine. This effect was partly reduced by Ca2+ withdrawal, and was abolished in the presence of tetrodotoxin (1 microM). The NMDA-receptor antagonist MK-801 (3 microM) attenuated the effect of hypoxia and hypoglycemia on [3H]DA release. It was suggested that activation of NMDA receptors is involved in dopamine release during hypoxia and energy deprivation.