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 (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 (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.
Highlights
In non-alcoholic drinkers, alcohol intake evokes acute release of dopamine in ventral striatum, as revealed in vivo by reduction of dopamine D2/3 receptor availability [1]
In one positron emission tomography (PET) study of alcoholism, detoxified alcoholic patients had significantly elevated influx of the DOPA decarboxylase substrate 6-[18F]fluoro-L-DOPA (FDOPA) to left putamen and right caudate nucleus [8], while in a subsequent study, detoxified alcoholic patients had no change of FDOPA uptake [9], a correlation was seen with alcohol craving
The mean magnitudes of K did not differ significantly between the groups, whereas in the group of alcoholics the mean magnitude of kloss was greater by 58% (P = 0.0003) and the mean magnitude of volume of distribution (Vd) was reduced by 43% (P = 0.002) (Table 1); there were no significant correlations between the triad of FDOPA kinetic parameters and the Alcohol Craving Questionnaire (ACQ) scores
Summary
In non-alcoholic drinkers, alcohol intake evokes acute release of dopamine in ventral striatum, as revealed in vivo by reduction of dopamine D2/3 receptor availability [1]. The competition between endogenous dopamine and exogenous tracer [11C]raclopride, estimated by means of positron emission tomography (PET), reveals attenuation of the dopamine release evoked by methylphenidate [5] or amphetamine [6]. These observations raise the question of changes in the dopamine synthesis capacity, which is one of the most robust indicators of psychotic states [7]. The ratio between the enzymatic clearance of FDOPA (K) and the rate of loss (kloss) constitutes a steady-state volume of distribution for the decarboxylated and deaminated metabolites, which reflects the total distribution volume in brain (Vd; ml g21), an index of dopamine storage capacity, as detailed in the earlier publications [19,20,21,22]
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