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. 2013 Sep 11;8(9):e73903.
doi: 10.1371/journal.pone.0073903. eCollection 2013.

Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients

Yoshitaka Kumakura  1 , Albert Gjedde, Daniele Caprioli, Thorsten Kienast, Anne Beck, Michail Plotkin, Florian Schlagenhauf, Ingo Vernaleken, Gerhard Gründer, Peter Bartenstein, Andreas Heinz, Paul Cumming
Affiliations

Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients

Yoshitaka Kumakura et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The parametric maps show mean steady-state storage capacity for FDOPA (Vd; ml g−1) in age-matched control subjects (A) and in abstinent patients with alcoholism (B), together with the subtraction map in horizontal (C) and coronal (D) planes projected onto the MNI brain atlas.
The t-maps show clusters of voxels with t >2.8 (E: green area) for the contrast between patients (N = 12) and age-matched healthy control subjects (N = 16), and the cluster of voxels with t >2.5 (F: green area) for the correlation between FDOPA-Vd and the individual score in the ACQ questionnaire of craving in the alcoholic group, accounting for the effect of the nuisance covariate (smoking).
Figure 2
Figure 2. The scatter plots show the correlation between acute alcohol craving and the magnitude of the fractional rate constant for elimination of [18F]-fluorodopamine formed in brain (upper: kloss, min−1), and steady-state storage of FDOPA and its decarboxylated metabolites (lower: Vd, ml g−1) for the left ventral striatum cluster.
The lines indicate simple linear regressions in these scatter plots.
See this image and copyright information in PMC

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Publication types

Grants and funding

This research was supported by grants from the University of Mainz and the State Rheinland-Pfalz, and by Denmark’s National Science Foundation and Medical Research Council. This research was also supported in part by Strategic International Cooperative Program, Japan Science and Technology Agency (JST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.