Rapid and reversible effects of methamphetamine on dopamine transporters.
Rapid and reversible effects of methamphetamine on dopamine transporters.
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发表时间：
1997-08
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通讯作者：
A. Fleckenstein;R. Metzger;Diana G. Wilkins;J. Gibb;G. Hanson
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作者：
A. Fleckenstein;R. Metzger;Diana G. Wilkins;J. Gibb;G. Hanson
体外实验中，活性氧降低了多巴胺转运体(DAT)的功能。鉴于此，并发现冰毒可在体内引起氧自由基的形成，我们研究了冰毒对大鼠纹状体DAT活性的影响。单次注射冰毒后1h，纹状体突触体的[~3H]多巴胺摄取呈剂量依赖性(0-15 mg/kg)下降；这种效应归因于[~3H]多巴胺摄取的Vmax降低。同样，多次大剂量注射冰毒(10 mg/kg/剂量，间隔2小时四次)会降低DAT功能。单次或多次注射冰毒后DAT活性的下降在治疗后24小时被逆转。冰毒处理对纹状体突触体内的5-羟色胺转运也有影响。综上所述，这些数据表明，冰毒降低DAT活性，可能是通过一种活性氧物种介导的机制。这些发现可能对氧化事件在单胺能系统的生理调节中的作用有重要的意义。
Reactive oxygen species decrease dopamine transporter (DAT) function in vitro. Because of this, and the finding that METH administration causes oxygen radical formation in vivo, the effects of METH administration on DAT activity in rat striatum were investigated. A single METH injection caused a dose-dependent (0-15 mg/kg) decrease in [3H]dopamine uptake into striatal synaptosomes prepared 1 h after METH administration; an effect attributable to a decreased Vmax of [3H]dopamine uptake. Similarly, multiple high-dose administrations of METH (10 mg/kg/dose; four doses at 2-h intervals) decreased DAT function. The decreases in DAT activity after either single or multiple METH administrations were reversed 24 h after treatment. [3H]5HT transport into striatal synaptosomes was also affected by METH treatment. Taken together, these data suggest that METH decreases DAT activity, perhaps through a reactive oxygen species-mediated mechanism. These findings may have important implications regarding the role of oxidative events in the physiological regulation of monoaminergic systems.