Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss
Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss
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DOI：
10.1016/s0006-8993(00)02439-2
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发表时间：
2000-07-21
期刊：
影响因子：
2.9
通讯作者：
Melega, WP
中科院分区：
文献类型：
--
作者：
Harvey, DC;Lacan, G;Melega, WP
在对黑长尾猴给予甲基苯丙胺（METH）（2 × 2：mg/kg，间隔6小时）后，在体内和死后研究中均观察到长期但可逆的多巴胺能缺陷。使用多巴胺转运蛋白（DAT）结合配体[C-11]WIN 35，428（WIN）进行的正电子发射断层扫描（PET）纵向研究显示，纹状体WIN结合在1周时降低80%，在1.5年时仅降低10%。其他METH受试者在1个月时的尸检特征显示，纹状体、内侧前脑束和腹侧中脑多巴胺（VMD）细胞区域中酪氨酸羟化酶（TH）、DAT和囊泡单胺转运蛋白-2（VMAT）的免疫反应性（IR）谱广泛降低。在1.5岁时，通过体视学方法评估，这些IR缺陷与VMD细胞数量的损失无关。此外，在1.5]耳，METH受试者的整个黑质纹状体多巴胺系统的IR曲线似乎与对照相似，尽管一些区域缺陷持续存在。总的来说，多巴胺能缺陷的幅度和程度，以及随后的恢复并不表明广泛的轴突变性，然后再生。或者，这种明显的可逆性的甲基诱导的神经适应可能主要与长期减少的VMD相关蛋白的表达，随着时间的推移恢复。(C)2000 Elsevier Science B. V.保留所有权利。
After administration of methamphetamine (METH) (2x2: mg/kg, 6 h apart) to vervet monkeys, long term but reversible dopaminergic deficits were observed in both in vivo and post-mortem studies. Longitudinal studies using positron emission tomography (PET) with the dopamine transporter (DAT)-binding ligand, [C-11]WIN 35,428 (WIN), were used to show decreases in striatal WIN binding of 80% at 1 week and only 10% at 1.5 years. A post-mortem characterization of other METH subjects at 1 month showed extensive decreases in immunoreactivity (IR) profiles of tyrosine hydroxylase (TH), DAT and vesicular monoamine transporter-2 (VMAT) in the striatum, medial forebrain bundle and the ventral midbrain dopamine (VMD) cell region. These IR deficits were not associated with a loss of VMD cell number when assessed at 1.5 years by stereological methods. Further, at 1.5],ears, IR profiles of METH subjects throughout the nigrostriatal dopamine system appeared similar to controls although some regional deficits persisted. Collectively, the magnitude and extent of the dopaminergic deficits, and the subsequent recovery were not suggestive of extensive axonal degeneration followed by regeneration. Alternatively, this apparent reversibility of the METH-induced neuroadaptations may be related primarily to long-term decreases in expression of VMD-related proteins that recover over time. (C) 2000 Elsevier Science B.V. All rights reserved.