Volkow N D, Chang L, Wang G J, Fowler J S, Franceschi D, Sedler M J, Gatley S J, Hitzemann R, Ding Y S, Wong C, Logan J
Department of Psychiatry, State University of New York at Stony Brook, USA.
Am J Psychiatry. 2001 Mar;158(3):383-9. doi: 10.1176/appi.ajp.158.3.383.
Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells.
Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [(18)F]fluorodeoxyglucose.
Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers.
The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.
甲基苯丙胺引发了人们的担忧，因为它可能对人类大脑具有神经毒性。尽管先前的研究主要集中在甲基苯丙胺对多巴胺能细胞的影响上，但有证据表明其他神经元类型也会受到影响。作者测量了区域脑葡萄糖代谢（它是脑功能的一个标志物），以评估在甲基苯丙胺滥用者中，除了多巴胺能细胞支配的区域之外，其他区域是否存在功能变化的证据。
15名已戒毒的甲基苯丙胺滥用者和21名对照受试者在注射[(18)F]氟脱氧葡萄糖后接受了正电子发射断层扫描。
甲基苯丙胺滥用者的全脑代谢比对照受试者高14%；差异在顶叶皮质最为明显（20%）。在对全脑代谢进行归一化后，甲基苯丙胺滥用者在丘脑（差异为17%）和纹状体（尾状核差异[12%]大于壳核[6%]）中的代谢显著降低。统计参数映射分析证实了这些发现，揭示甲基苯丙胺滥用者顶叶皮质代谢较高，丘脑和纹状体代谢较低。
顶叶皮质是一个没有任何显著多巴胺能神经支配的区域，这一事实表明，甲基苯丙胺滥用者该区域较高的代谢是甲基苯丙胺在多巴胺调节之外的神经回路中产生作用的结果。此外，纹状体和丘脑（多巴胺信号传入皮质的主要输出部位）较低的代谢可能反映了甲基苯丙胺在多巴胺能神经回路中的功能后果。这些结果提供了证据，表明在人类中，甲基苯丙胺滥用会导致多巴胺能和非多巴胺能支配的脑区功能发生变化。
