Methamphetamine decreases mouse striatal dopamine transporter activity: roles of hyperthermia and dopamine.
Methamphetamine decreases mouse striatal dopamine transporter activity: roles of hyperthermia and dopamine.
复制标题
甲基苯丙胺降低小鼠纹状体多巴胺转运蛋白活性：高温和多巴胺的作用。
DOI：
10.1016/s0014-2999(00)00871-2
复制
发表时间：
2000
影响因子：
5
通讯作者：
Fleckenstein,AE
中科院分区：
文献类型：
--
作者：
Sandoval,V;Hanson,GR;Fleckenstein,AE
多次给予甲基苯丙胺可迅速降低大鼠纹状体多巴胺转运蛋白的活性。为了确定这种现象的物种特异性，本研究检测了这种兴奋剂对小鼠体内多巴胺转运体的影响。与大鼠一样，多次注射甲基苯丙胺迅速降低了纹状体多巴胺转运蛋白的活性；这种下降在24小时后被部分逆转。此外，甲基苯丙胺减少了多巴胺转运蛋白配体WIN35428的结合，但程度低于多巴胺转运蛋白功能的变化。这些下降似乎不是由于最初的药物治疗引入的残留甲基苯丙胺造成的。与老鼠一样，体温过高也导致了这种现象。与大鼠不同，在小鼠中没有观察到多巴胺的作用，因为α-甲基-对酪氨酸预处理导致的多巴胺耗竭并不能阻止这种下降。此外，与大鼠不同的是，用多巴胺D1或D2受体拮抗剂(分别为SCH23390或乙硫氯必利)预处理并不能减弱甲基苯丙胺引起的多巴胺摄取减少。这些发现表明，甲基苯丙胺对小鼠和大鼠多巴胺转运体功能的急性影响既有相似之处，也有不同之处，并建议将小鼠作为评估甲基苯丙胺对多巴胺转运体急性影响的额外模型。
Multiple methamphetamine administrations rapidly decrease rat striatal dopamine transporter activity. To determine the species specificity of this phenomenon, the present studies examined effects of this stimulant on the dopamine transporter in mice. As in rats, multiple methamphetamine injections rapidly reduced striatal dopamine transporter activity; a decrease that was partially reversed 24 h later. Moreover, methamphetamine decreased binding of the dopamine transporter ligand, WIN35428, but to a lesser degree than the change in dopamine transporter function. These decreases did not appear to result from residual methamphetamine introduced by the original drug treatment. As in rats, hyperthermia contributed to this phenomenon. Unlike in rats, a role for dopamine was not observed in mice as dopamine depletion, resulting from α-methyl-p-tyrosine pretreatment, did not prevent this decrease. In addition, unlike in rats, pretreatment with either a dopamine D1or D2receptor antagonist (SCH23390 or eticlopride, respectively) did not attenuate the methamphetamine-induced reduction in dopamine uptake. These findings demonstrate both similarities and differences in the acute effects of methamphetamine on dopamine transporter function in mice and rats, and suggest the mouse as an additional model for assessing the acute effects of methamphetamine on the dopamine transporter.