Single and binge methamphetamine administrations have different effects on the levels of dopamine D2 autoreceptor and dopamine transporter in rat striatum.
Single and binge methamphetamine administrations have different effects on the levels of dopamine D2 autoreceptor and dopamine transporter in rat striatum.
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DOI：
10.3390/ijms15045884
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发表时间：
2014-04-08
影响因子：
5.6
通讯作者：
Moszczynska A
中科院分区：
文献类型：
--
作者：
Chauhan H;Killinger BA;Miller CV;Moszczynska A
甲基苯丙胺（冰毒）是一种中枢神经系统精神兴奋剂，具有很高的滥用潜力。在高剂量下，甲基苯丙胺会导致纹状体中多巴胺能末端的选择性退化。多巴胺D2受体拮抗剂和多巴胺转运蛋白（DAT）抑制剂通过降低细胞内多巴胺含量，从而减少多巴胺自氧化和活性氧的产生，从而防止药物的神经毒性。在体外，安非他明通过调节D2受体和DAT的细胞内运输来调节它们的功能。没有关于这两种蛋白轴突转运的数据，它们在体内相互作用的数据也有限。本研究的目的是检测两种不同的甲基安非他明方案后突触前D2自身受体和DAT的突触体水平，并确定甲基安非他明是否影响大鼠纹状体中D2自身受体-DAT的相互作用。我们发现，与生理盐水对照相比，单次高剂量冰毒降低了大鼠纹状体突触体D2自身受体的免疫反应性，增加了DAT的免疫反应性，而暴食高剂量冰毒增加了D2自身受体的免疫反应性，对DAT的免疫反应性没有影响。单一冰毒对D2自受体- dat相互作用没有影响，而暴食冰毒增加了纹状体中两种蛋白质之间的相互作用。我们的研究结果表明，甲基安非他明可以以相互依赖和独立的方式影响D2自身受体和DAT的轴突运输。
Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum. Dopamine D2 receptor antagonists and dopamine transporter (DAT) inhibitors protect against neurotoxicity of the drug by decreasing intracellular dopamine content and, consequently, dopamine autoxidation and production of reactive oxygen species. In vitro, amphetamines regulate D2 receptor and DAT functions via regulation of their intracellular trafficking. No data exists on axonal transport of both proteins and there is limited data on their interactions in vivo. The aim of the present investigation was to examine synaptosomal levels of presynaptic D2 autoreceptor and DAT after two different regimens of METH and to determine whether METH affects the D2 autoreceptor-DAT interaction in the rat striatum. We found that, as compared to saline controls, administration of single high-dose METH decreased D2 autoreceptor immunoreactivity and increased DAT immunoreactivity in rat striatal synaptosomes whereas binge high-dose METH increased immunoreactivity of D2 autoreceptor and had no effect on DAT immunoreactivity. Single METH had no effect on D2 autoreceptor-DAT interaction whereas binge METH increased the interaction between the two proteins in the striatum. Our results suggest that METH can affect axonal transport of both the D2 autoreceptor and DAT in an interaction-dependent and -independent manner.
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DOI：
10.1523/jneurosci.4858-08.2009
发表时间：
2009-01-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bertolino A;Fazio L;Di Giorgio A;Blasi G;Romano R;Taurisano P;Caforio G;Sinibaldi L;Ursini G;Popolizio T;Tirotta E;Papp A;Dallapiccola B;Borrelli E;Sadee W
通讯作者：
Sadee W
影响因子：
4.7
作者：
Boudanova, Ekaterina;Navaroli, Deanna A.;Melikian, Haley E.
通讯作者：
Melikian, Haley E.
影响因子：
3.1
作者：
Fuxe, K;Ferré, S;Franco, R
通讯作者：
Franco, R
影响因子：
3.7
作者：
Beauvais G;Atwell K;Jayanthi S;Ladenheim B;Cadet JL
通讯作者：
Cadet JL
影响因子：
11.4
作者：
DALTOSO, R;SOMMER, B;SEEBURG, PH
通讯作者：
SEEBURG, PH