title: Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients.
abstract: A previous study of the DOPA decarboxylase substrate 6-[(18)F]fluoro-L-DOPA (FDOPA) with positron emission tomography (PET) detected no difference of the net blood-brain transfer rate (Kin(app)) between detoxified alcoholic patients and healthy controls. Instead, the study revealed an inverse correlation between Kin (app) in left ventral striatum and alcohol craving scores. To resolve the influx and efflux phases of radiolabeled molecules, we independently estimated the unidirectional blood-brain FDOPA clearance rate (K) and the washout rate of [(18)F]fluorodopamine and its deaminated metabolites (k(loss)), and we also calculated the total distribution volume of decarboxylated metabolites and unmetabolized FDOPA as a steady-state index of the dopamine storage capacity (V(d)) in brain. The craving scores in the 12 alcoholics correlated positively with the rate of loss (k(loss)) in the left ventral striatum. We conclude that craving is most pronounced in the individuals with relatively rapid dopamine turnover in the left ventral striatum. The blood-brain clearance rate (K), corrected for subsequent loss of radiolabeled molecules from brain, was completely normal throughout the brain of the alcoholics, in whom the volume of distribution (V(d)) was found to be significantly lower in the left caudate nucleus. The magnitude of Vd in the left caudate head was reduced by 43% relative to the 16 controls, consistent with a 58% increase of k(loss). We interpret the findings as indicating that a trait for rapid dopamine turnover in the ventral striatum subserves craving and reward-dependence, leading to an acquired state of increased dopamine turnover in the dorsal striatum of detoxified alcoholic patients.
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark ; Center for Functionally Integrative Neuroscience, Aarhus University, Aarhus C, Denmark ; Department of Nuclear Medicine, Tokyo University, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumakura
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.forename: Daniele
authors.initials: D
authors.lastname: Caprioli
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kienast
authors.forename: Anne
authors.initials: A
authors.lastname: Beck
authors.forename: Michail
authors.initials: M
authors.lastname: Plotkin
authors.forename: Florian
authors.initials: F
authors.lastname: Schlagenhauf
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000378:metabolism*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography
chemical_list: D004298:Dopamine
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