title: Increased vesicular monoamine transporter binding during early abstinence in human methamphetamine users: Is VMAT2 a stable dopamine neuron biomarker?
abstract: 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 [(11)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 [(11)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 We measured striatal VMAT2 binding in 16 recently withdrawn (mean, 19 d; range, 1-90 d) methamphetamine users and in 14 healthy matched-control subjects during a PET scan with (+)[(11)C]DTBZ. Unexpectedly, striatal (+)[(11)C]DTBZ binding was increased in methamphetamine users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral striatum). Increased (+)[(11)C]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 (+)[(11)C]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 (+)[(11)C]DTBZ binding is that VMAT2 binding is sensitive to changes in vesicular dopamine storage levels, presumably low in drug users. If correct, (+)[(11)C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine.
authors.affiliation: Human Neurochemical Pathology Laboratory, University of Toronto, Toronto, Ontario, Canada. isabelle_boileau@camh.net
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Diana
authors.initials: D
authors.lastname: Wilkins
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.forename: Mark
authors.initials: M
authors.lastname: Guttman
authors.forename: Jean A
authors.initials: JA
authors.lastname: Saint-Cyr
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008875:Middle Aged; D009460:Neurologic Examination / Q000379:methods; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D008694:Methamphetamine; D013747:Tetrabenazine