当前位置： SCI文献检索 > BRAIN RESEARCH期刊下所有文献 > The effects of monoamine uptake inhibitors and methamphetamine on neostriatal 6-hydroxydopamine (6-OHDA) formation, short-term monoamine depletions and locomotor activity in the rat.

The effects of monoamine uptake inhibitors and methamphetamine on neostriatal 6-hydroxydopamine (6-OHDA) formation, short-term monoamine depletions and locomotor activity in the rat.

Abstract：

:Monoamine uptake inhibitors block the neurotoxic effects of methamphetamine (MA) upon dopaminergic and serotonergic neurons in the rat. The neurotoxic effects of MA upon dopaminergic neurons have previously been suggested to be mediated via formation of 6-hydroxydopamine (6-OHDA) from endogenous stores of dopamine (DA). In the present experiments, administration of the DA uptake inhibitor amfonelic acid (AFA, 10 mg/kg, i.p.) did not block the formation of 6-OHDA in rats treated with a single s.c. 100 mg/kg dose of MA. Consistent with the lack of effect by AFA on MA-induced 6-OHDA formation, neither AFA (10 mg/kg, i.p.) nor the DA and 5-hydroxytryptamine (5-HT) uptake inhibitor mazindol (40 mg/kg i.p., MAZ) blocked the depletion seen in neostriatal DA levels 1, 2 or 8 h following administration of a single 100 mg/kg dose of MA. In fact, AFA enhanced the DA depletions 2 and 8 h following MA administration. AFA also enhanced the MA-induced increase in locomotor activity in rats and this effect was blocked by lesions of dopaminergic neurons with i.v.t. (intraventricular) 6-OHDA in desipramine-pretreated rats. These results suggest that DA uptake inhibitors do not prevent the neurotoxic effect of MA on DA neurons by either preventing entry of MA into the cell or blocking the efflux of DA out of the cell. Instead, the DA uptake inhibitors appear to prevent the neurotoxic effect of MA upon dopaminergic neurons by blocking entry of 6-OHDA into the cell.

journal_name

Brain Res

journal_title

Brain research

authors

Marek GJ,Vosmer G,Seiden LS

doi

10.1016/0006-8993(90)90889-j

subject

Has Abstract

pub_date

1990-05-14 00:00:00

pages

1-7

issue

1

eissn

0006-8993

issn

1872-6240

pii

0006-8993(90)90889-J

journal_volume

516

pub_type

杂志文章

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