ALPHA-METHYL-P-TYROSINE PRETREATMENT PARTIALLY PREVENTS METHAMPHETAMINE-INDUCED ENDOGENOUS NEUROTOXIN FORMATION
ALPHA-METHYL-P-TYROSINE PRETREATMENT PARTIALLY PREVENTS METHAMPHETAMINE-INDUCED ENDOGENOUS NEUROTOXIN FORMATION
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DOI：
10.1016/0006-8993(90)90606-c
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发表时间：
1990-05-07
期刊：
影响因子：
2.9
通讯作者：
SEIDEN, LS
中科院分区：
文献类型：
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作者：
AXT, KJ;COMMINS, DL;SEIDEN, LS
用酪氨酸羟化酶抑制剂α-甲基-对酪氨酸(AMT)预处理脑多巴胺(DA)可以防止甲基苯丙胺(MA)的长期神经毒性作用。此外，最近有报道称，神经毒素6-羟基多巴胺(6-OHDA)和5，6-二羟色胺(5，6-DHT)分别在单次神经毒性剂量MA后在新纹状体和海马区内源性形成。因此，我们考察了AMT预处理防止MA诱导的6-OHDA和5，6-DHT形成的能力。我们报道，AMT预处理显著降低了MA给药后6-OHDA和5，6-DHT的检测频率。在MA给药2周后，将神经毒素的形成与脑中DA和5-羟色胺(5-HT)的水平进行比较。结论：AMT能够抑制6-OHDA的形成和DA的长期消耗是由于MA可释放库的减少。AMT对MA引起的5-羟色胺缺乏的影响尚不清楚，可能涉及其他因素。
Depletion of brain dopamine (DA) by pretreatment with the tyrosine hydroxylase inhibitor .alpha.-methyl-p-tyrosine (AMT) has been shown to prevent the long-term neurotoxic effects of methamphetamine (MA). In addition, it has recently been reported that the neurotoxins 6-hydroxydopamine (6-OHDA) and 5,6-dihydroxytryptamine (5,6-DHT) are formed endogenously in neostriatum and hippocampus, respectively, following a single neurotoxic dose of MA. We, therefore, have examined the ability of AMT pretreatment to prevent the MA-induced formation of 6-OHDA and 5,6-DHT. We report that AMT pretreatment significantly decreases the frequency with which 6-OHDA and 5,6-DHT are detected following MA administration. Neurotoxin formation is compared with brain levels of DA and 5-hydroxytryptamine (5-HT) 2 weeks after MA administration. It is concluded that the ability of AMT to attenuate both 6-OHDA formation and long-term depletions of DA is due to a decrease in the MA-releasable pool of DA. The effect of AMT on MA-induced depletions of 5-HT is less clear and may involve additional factors.