title: Effects of Smoking Cessation on Presynaptic Dopamine Function of Addicted Male Smokers.
abstract: There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence.
  
  
  
  We obtained baseline 6-[(18)F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence (n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (kloss); and the tracer distribution volume (Vd), which is an index of dopamine storage capacity.
  
  
  
  Compared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, Vd significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers.
  
  
  
  The results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen; Department of Psychiatry and Psychotherapy, Social Neuroscience Laboratory, University of Lübeck, Lübeck, Germany. Electronic address: Rademacher@snl.uni-luebeck.de.
authors.forename: Lena
authors.initials: L
authors.lastname: Rademacher
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen; Department of Psychiatry and Psychotherapy, Centre for Integrative Psychiatry, University of Zürich, Rheinau, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Prinz
authors.affiliation: Department of Nuclear Medicine, RWTH Aachen University, Aachen.
authors.forename: Oliver
authors.initials: O
authors.lastname: Winz
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen.
authors.forename: Karsten
authors.initials: K
authors.lastname: Henkel
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Dietrich
authors.affiliation: Department of Nuclear Medicine, RWTH Aachen University, Aachen.
authors.forename: Jörn
authors.initials: J
authors.lastname: Schmaljohann
authors.affiliation: Department of Nuclear Medicine, RWTH Aachen University, Aachen.
authors.forename: Siamak
authors.initials: S
authors.lastname: Mohammadkhani Shali
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen.
authors.forename: Ina
authors.initials: I
authors.lastname: Schabram
authors.affiliation: Department of Anesthesiology, RWTH Aachen University, Aachen; Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen.
authors.forename: Christian
authors.initials: C
authors.lastname: Stoppe
authors.affiliation: Department of Neuropsychiatry and Psychosomatic Medicine, Oslo University Hospital, Oslo, Norway; School of Psychology and Counselling, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.affiliation: Department of Medical Statistics, RWTH Aachen University, Aachen.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hilgers
authors.affiliation: Department of Pharmacology and Neuroscience, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumakura
authors.affiliation: Department of Anesthesiology, RWTH Aachen University, Aachen.
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
authors.affiliation: Department of Nuclear Medicine, RWTH Aachen University, Aachen; Jülich/Aachen Research Alliance, Aachen, Germany; Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen; Jülich/Aachen Research Alliance, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen; Jülich/Aachen Research Alliance, Aachen, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007700:Kinetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D055815:Young Adult
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine
keywords: Abstinence; Dopamine; FDOPA; Nicotine dependence; Smoking cessation; Striatum