Abstract
We tested the ability of the non-competitive N-methyl- d-aspartate (NMDA) antagonist, dizocilpine (MK-801), to promote protection against the acute effect of 1-methyl-4-phenylpyridinium ion (MPP +) in rat striatal slices. Pretreatment with MK-801 at concentrations higher than 15 μM partially prevented the dopamine (DA)-depleting effect induced by further incubation with 25 μM MPP + for 60 min in Mg 2+-free conditions. Incubation of slices with 15 μM MK-801 without MPP + only affected the levels of 3-methoxytyramine (3-MT). The ratio of 3-MT to 3,4-dihydroxyphenylacetic acid (DOPAC), a proposed index of DA reuptake inhibition, increased +68% of control levels, clearly suggesting an inhibitory effect of MK-801 on the high affinity DA transport system. To test this possibility, we performed a dose-response study of MK-801 on the high-affinity DA transport system in rat striatal synaptosomes. MK-801 induced a dose-dependent inhibition of DA uptake, with an ic 50 of 57.0 μM. We present evidence that the protective effect rendered by MK-801 against the acute DA-depleting effect induced by MPP + is not associated to NMDA receptor function, but rather to an inhibition of the high affinity DA uptake system. Copyright © 1996 Elsevier Science Ltd.
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