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  Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients

Kumakura, Y., Gjedde, A., Caprioli, D., Kienast, T., Beck, A., Plotkin, M., et al. (2013). Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients. PLoS One, 8(9): e73903. doi:10.1371/journal.pone.0073903.

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© 2013 Kumakura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 Creators:
Kumakura, Yoshitaka1, 2, Author
Gjedde, Albert1, 2, Author
Caprioli, Daniele3, Author
Kienast, Thorsten4, Author
Beck, Anne4, Author
Plotkin, Michail5, Author
Schlagenhauf, Florian4, 6, Author           
Vernaleken, Ingo7, Author
Gründer, Gerhard7, Author
Bartenstein, Peter8, Author
Heinz, Andreas4, Author
Cumming, Paul8, Author
Affiliations:
1Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark, ou_persistent22              
2Center of Functionally Integrative Neuroscience, Aarhus University, Denmark, ou_persistent22              
3Department of Nuclear Medicine, University of Tokyo, Japan, ou_persistent22              
4Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany, ou_persistent22              
5Department of Nuclear Medicine, Charité University Medicine Berlin, Germany, ou_persistent22              
6Max Planck Fellow Group Cognitive and Affective Control of Behavioural Adaptation, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_1753350              
7Department of Psychiatry, Psychotherapy, and Psychosomatics, RWTH Aachen University, Germany, ou_persistent22              
8Department of Nuclear Medicine, Ludwig Maximilians University Munich, Germany, ou_persistent22              

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 Abstract: A previous study of the DOPA decarboxylase substrate 6-[18F]fluoro-L-DOPA (FDOPA) with positron emission tomography (PET) detected no difference of the net blood-brain transfer rate (Kinapp) between detoxified alcoholic patients and healthy controls. Instead, the study revealed an inverse correlation between Kinapp 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 [18F]fluorodopamine and its deaminated metabolites (kloss), and we also calculated the total distribution volume of decarboxylated metabolites and unmetabolized FDOPA as a steady-state index of the dopamine storage capacity (Vd) in brain. The craving scores in the 12 alcoholics correlated positively with the rate of loss (kloss) 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 (Vd) 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 kloss. 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.

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Language(s): eng - English
 Dates: 2013-04-042013-07-252013-09-11
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pone.0073903
PMID: 24040111
PMC: PMC3770672
Other: eCollection 2013
 Degree: -

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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 8 (9) Sequence Number: e73903 Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850