MULTIPLE METHAMPHETAMINE INJECTIONS INDUCE MARKED INCREASES IN EXTRACELLULAR STRIATAL DOPAMINE WHICH CORRELATE WITH SUBSEQUENT NEUROTOXICITY
MULTIPLE METHAMPHETAMINE INJECTIONS INDUCE MARKED INCREASES IN EXTRACELLULAR STRIATAL DOPAMINE WHICH CORRELATE WITH SUBSEQUENT NEUROTOXICITY
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DOI：
10.1016/0006-8993(91)91461-9
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发表时间：
1991-11-15
期刊：
影响因子：
2.9
通讯作者：
MARSHALL, JF
中科院分区：
文献类型：
--
作者：
ODELL, SJ;WEIHMULLER, FB;MARSHALL, JF
急性期，甲基苯丙胺（m-AMPH）被认为是刺激多巴胺（DA）在纹状体的净流出，同时抑制DA的摄取，从而产生高浓度的DA细胞外。重复给药m-AMPH已被证明损害DA终端在纹状体。然而，很少有直接的信息存在间-AMPH诱导的DA溢出和神经毒性之间的关系。在本研究中，我们使用在体微透析来探索这个话题。四，但不是3，注射m-AMPH（4毫克/公斤，sc，在2小时的间隔）损坏纹状体DA末梢测量的43-51%减少死后纹状体DA含量1周后。在清醒的动物纹状体微透析过程中的m-AMPH治疗表明，DA溢出增加后，每一个m-AMPH注射，但约1.5小时后，第四次m-AMPH注射，DA溢出发生显着增加，显着大于后所看到的任何前3次注射。此外，在接受4次m-AMPH注射的动物中，累积的DA溢出与1周后纹状体DA含量呈负相关（r =-0.74，P < 0.05），表明在第4次m-AMPH注射后观察到的大量DA溢出在m-AMPH神经毒性中尤其重要。
Acutely, methamphetamine (m-AMPH) is known to stimulate a net efflux of dopamine (DA) in the striatum while inhibiting DA uptake, thus producing high extracellular concentrations of DA. Repeated administration of m-AMPH has been shown to damage DA terminals in the striatum. However, little direct information exists about the relationship between m-AMPH-induced DA overflow and neurotoxicity. In the present study, we used in vivo microdialysis to explore this topic. Four, but not 3, injections of m-AMPH (4 mg/kg, sc, at 2 h intervals) damaged striatal DA terminals as measured by a 43-51% decrease in post mortem striatal DA content 1 week later. Striatal microdialysis in awake animals during the course of m-AMPH treatment showed that DA overflow increased after each m-AMPH injection, but that approximately 1.5 h after the fourth m-AMPH injection, a striking increase in DA overflow occurred that was significantly larger than that seen after any of the previous 3 injections. Additionally, in animals receiving 4 injections of m-AMPH, cumulative DA overflow was negatively correlated with striatal DA content 1 week later (r = -0.74, P < 0.05), suggesting that the substantial DA overflow seen after the fourth m-AMPH injection is especially important in m-AMPH neurotoxicity.