title: Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence.
abstract: We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [(11)C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [(11)C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication.
authors: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Isabelle
authors: I
authors: Boileau
authors: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Tina
authors: T
authors: McCluskey
authors: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Junchao
authors: J
authors: Tong
authors: Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: Yoshiaki
authors: Y
authors: Furukawa
authors: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Sylvain
authors: S
authors: Houle
authors: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
authors: Stephen J
authors: SJ
authors: Kish
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D003042:Cocaine / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D049268:Positron-Emission Tomography; D013572:Synaptic Vesicles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D013747:Tetrabenazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; C032811:dihydrotetrabenazine; D008694:Methamphetamine; D003042:Cocaine; D004298:Dopamine; D013747:Tetrabenazine