Methamphetamine rapidly decreases vesicular dopamine uptake
Methamphetamine rapidly decreases vesicular dopamine uptake
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DOI：
10.1046/j.1471-4159.2000.0742221.x
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发表时间：
2000-05-01
影响因子：
4.7
通讯作者：
Fleckenstein, AE
中科院分区：
文献类型：
--
作者：
Brown, JM;Hanson, GR;Fleckenstein, AE
囊泡隔离在调节单胺如多巴胺的细胞质浓度中是重要的。此外，最近的证据表明，细胞质多巴胺水平的增加，可能归因于囊泡单胺转运蛋白功能的变化，有助于甲基苯丙胺诱导的多巴胺能缺陷。因此，我们研究了甲基苯丙胺治疗后纹状体囊泡摄取是否改变。甲基苯丙胺的多次给药迅速（1小时内）减少囊泡多巴胺摄取和二氢丁苯那嗪结合，这种作用（a）持续至少24小时，（B）与多巴胺而不是5-羟色胺神经元相关，（c）与最初甲基苯丙胺治疗引入的残留药物无关。这些数据表明，甲基苯丙胺迅速降低多巴胺能神经元的囊泡单胺转运体功能，这种现象可能与这种兴奋剂引起的长期损害有关。
Vesicular sequestration is important in the regulation of cytoplasmic concentrations of monoamines such as dopamine. Moreover, recent evidence suggests that increases in cytoplasmic dopamine levels, perhaps attributable to changes in vesicular monoamine transporter function, contribute to methamphetamine-induced dopaminergic deficits. Hence, we examined whether striatal vesicular uptake is altered following methamphetamine treatment. Multiple administrations of methamphetamine rapidly (within 1 h) decreased vesicular dopamine uptake and dihydrotetrabenazine binding, an effect that (a) persisted at least 24 h, (b) was associated with dopamine and not serotonin neurons, and (c) was unrelated to residual drug introduced by the original methamphetamine treatment. These data suggest that methamphetamine rapidly decreases vesicular monoamine transporter function in dopaminergic neurons, a phenomenon that may be associated with the long-term damage caused by this stimulant.