Increased vesicular monoamine transporter binding during early abstinence in human methamphetamine users: Is VMAT2 a stable dopamine neuron biomarker?

被引:68
作者
Boileau, Isabelle [1 ]
Rusjan, Pablo [2 ]
Houle, Sylvain [2 ]
Wilkins, Diana
Tong, Junchao
Selby, Peter [3 ]
Guttman, Mark [2 ,3 ,4 ,5 ,6 ]
Saint-Cyr, Jean A. [5 ]
Wilson, Alan A. [2 ]
Kish, Stephen J.
机构
[1] Univ Toronto, Ctr Addict & Mental Hlth, Human Neurochem Pathol Lab, Toronto, ON M5T 1R8, Canada
[2] Univ Toronto, Vivian M Rakoff PET Imaging Ctr, Toronto, ON M5T 1R8, Canada
[3] Univ Toronto, Ctr Addict & Mental Hlth, Addict Program, Toronto, ON M5T 1R8, Canada
[4] Univ Utah, Ctr Human Toxicol, Salt Lake City, UT 84101 USA
[5] Univ Toronto, Toronto Western Res Inst, Div Brain Imaging & Behav Syst, Toronto, ON M5G 2M9, Canada
[6] Ctr Movement Disorders, Markham, ON L6B 1C9, Canada
关键词
vesicular monoamine transporter 2; positron emission tomography; dihydrotetrabenazine; methamphetamine; dopamine monoamine;
D O I
10.1523/JNEUROSCI.3008-08.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Animal data indicate that methamphetamine can damage striatal dopamine terminals. Efforts to document dopamine neuron damage in living brain of methamphetamine users have focused on the binding of [C-11] dihydrotetrabenazine (DTBZ), a vesicular monoamine transporter (VMAT2) positron emission tomography (PET) radioligand, as a stable dopamine neuron biomarker. Previous PET data report a slight decrease in striatal [ 11C] DTBZ binding in human methamphetamine users after prolonged ( mean, 3 years) abstinence, suggesting that the reduction would likely be substantial in early abstinence. We measured striatal VMAT2 binding in 16 recently withdrawn (mean, 19 d; range, 1-90 d) methamphetamine users and in 14 healthy matched-control subjects during a PET scan with (+)[C-11] DTBZ. Unexpectedly, striatal (+)[C-11]DTBZ binding was increased in methamphetamine users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral striatum). Increased (+)[ 11C] DTBZ binding in caudate was most marked in methamphetamine users abstinent for 1-3 d (+41%), relative to the 7-21 d (+15%) and >21 d (+9%) groups. Above-normal VMAT2 binding in some drug users suggests that any toxic effect of methamphetamine on dopamine neurons might be masked by an increased (+)[C-11] DTBZ binding and that VMAT2 radioligand binding might not be, as is generally assumed, a "stable" index of dopamine neuron integrity in vivo. One potential explanation for increased (+)[C-11] DTBZ binding is that VMAT2 binding is sensitive to changes in vesicular dopamine storage levels, presumably low in drug users. If correct, (+)[C-11] DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine.
引用
收藏
页码:9850 / 9856
页数:7
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