Volkow N D, Chang L, Wang G J, Fowler J S, Leonido-Yee M, Franceschi D, Sedler M J, Gatley S J, Hitzemann R, Ding Y S, Logan J, Wong C, Miller E N
Department of Psychiatry, State University of New York at Stony Brook, USA.
Am J Psychiatry. 2001 Mar;158(3):377-82. doi: 10.1176/appi.ajp.158.3.377.
Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant.
Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function.
Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment.
These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.
甲基苯丙胺是一种流行且极易成瘾的滥用药物，因其在实验动物中已被证明对多巴胺末梢具有神经毒性而引发关注。作者评估了人类是否会出现类似变化，并评估这些变化是否具有功能上的显著性。
在给予[(11)C]d-苏式-甲基苯丙胺（一种多巴胺转运体配体）后进行正电子发射断层扫描，测量了15名戒毒后的甲基苯丙胺滥用者和18名对照者大脑中的多巴胺转运体水平（多巴胺细胞末梢的标志物）。还进行了神经心理学测试以评估运动和认知功能。
与对照者相比，甲基苯丙胺滥用者纹状体中的多巴胺转运体显著减少（尾状核平均差异为27.8%，壳核为21.1%）；即使在戒毒至少11个月的滥用者中这种减少也很明显。多巴胺转运体减少与运动迟缓及记忆损害有关。
这些结果提供了证据，表明人类滥用甲基苯丙胺所服用的剂量会导致多巴胺转运体减少，这与运动和认知损害相关。这些结果强调了提醒临床医生和公众注意甲基苯丙胺可在人脑中诱发的长期变化的紧迫性。
