Brown J M, Hanson G R, Fleckenstein A E
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
J Neurochem. 2000 May;74(5):2221-3. doi: 10.1046/j.1471-4159.2000.0742221.x.
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.
囊泡隔离在调节多巴胺等单胺类物质的细胞质浓度方面很重要。此外，最近的证据表明，细胞质多巴胺水平的升高，可能归因于囊泡单胺转运体功能的变化，会导致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发生改变。多次给予甲基苯丙胺可迅速（在1小时内）降低囊泡多巴胺摄取和二氢四苯嗪结合，这种效应（a）至少持续24小时，（b）与多巴胺神经元而非5-羟色胺神经元有关，（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，甲基苯丙胺会迅速降低多巴胺能神经元中囊泡单胺转运体的功能，这一现象可能与这种兴奋剂造成的长期损害有关。
