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Efforts to document dopamine neuron damage in living brain of methamphetamine users have focused on the binding of [<jats:sup>11<\/jats:sup>C]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 [<jats:sup>11<\/jats:sup>C]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 We measured striatal VMAT2 binding in 16 recently withdrawn (mean, 19 d; range, 1\u201390 d) methamphetamine users and in 14 healthy matched-control subjects during a PET scan with (+)[<jats:sup>11<\/jats:sup>C]DTBZ. Unexpectedly, striatal (+)[<jats:sup>11<\/jats:sup>C]DTBZ binding was increased in methamphetamine users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral striatum). Increased (+)[<jats:sup>11<\/jats:sup>C]DTBZ binding in caudate was most marked in methamphetamine users abstinent for 1\u20133 d (+41%), relative to the 7\u201321 d (+15%) and &gt;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 (+)[<jats:sup>11<\/jats:sup>C]DTBZ binding and that VMAT2 radioligand binding might not be, as is generally assumed, a \u201cstable\u201d index of dopamine neuron integrity<jats:italic>in vivo<\/jats:italic>. One potential explanation for increased (+)[<jats:sup>11<\/jats:sup>C]DTBZ binding is that VMAT2 binding is sensitive to changes in vesicular dopamine storage levels, presumably low in drug users. If correct, (+)[<jats:sup>11<\/jats:sup>C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine.<\/jats:p>","DOI":"10.1523\/jneurosci.3008-08.2008","type":"journal-article","created":{"date-parts":[[2008,9,24]],"date-time":"2008-09-24T16:28:23Z","timestamp":1222273703000},"page":"9850-9856","source":"Crossref","is-referenced-by-count":87,"title":["Increased Vesicular Monoamine Transporter Binding during Early Abstinence In Human Methamphetamine Users: Is VMAT2 a Stable Dopamine Neuron 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