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MK-801 partially protects against the acute MPP+ depleting effect on dopamine levels in rat striatal slices.

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 microM partially prevented the dopamine (DA)-depleting effect induced by further incubation with 25 microM MPP+ for 60 min in Mg(2+)-free conditions. Incubation of slices with 15 microM 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 IC50 of 57.0 microM. 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.

journal_name

Neurochem Int

journal_title

Neurochemistry international

authors

Venero JL,Santiago M,Machado A,Cano J

doi

10.1016/0197-0186(95)00163-8

subject

Has Abstract

pub_date

1996-10-01 00:00:00

pages

411-6

issue

4

eissn

0197-0186

issn

1872-9754

pii

0197-0186(95)00163-8

journal_volume

29

pub_type

杂志文章

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