Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients.
OBJECTIVE
In abstinent alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of craving for alcohol. Alcohol craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy comparison subjects.


METHODS
Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 alcoholic patients and in 12 of the healthy volunteers. Alcohol craving was measured with the Alcohol Craving Questionnaire. Patients were followed for 6 months, and alcohol intake was recorded.


RESULTS
The magnitude of net blood-brain clearance in the striatum did not differ significantly between detoxified alcoholic patients and the comparison subjects. However, a voxel-wise correlation analysis of net blood-brain clearance in the alcoholic patients linked low levels of dopamine synthesis capacity in the bilateral putamen with high levels of alcohol craving. After normalization of net blood-brain clearance maps to the voxel-wise estimates of dopamine D2/3 receptor availability, there was still a negative correlation with alcohol craving. Alcohol craving at the time of scanning was associated with high level of alcohol intake in the 6-month follow-up period.


CONCLUSIONS
Simultaneous assay by PET of pre- and postsynaptic markers of dopamine neurotransmission indicated that a striatal dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk.
Heinz
Andreas
A
Central Institute of Mental Health, Mannheim, Germany.
Siessmeier
Thomas
T
Wrase
Jana
J
Buchholz
Hans Georg
HG
Gründer
Gerhard
G
Kumakura
Yoshitaka
Y
Cumming
Paul
P
Schreckenberger
Mathias
M
Smolka
Michael N
MN
Rösch
Frank
F
Mann
Karl
K
Bartenstein
Peter
P
D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D016739:Behavior, Addictive / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis* / Q000502:physiology; D015259:Dopamine Agents / Q000378:metabolism; D005462:Fluorine Radioisotopes; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism* / Q000502:physiology; D050637:Receptors, Dopamine D3; D012008:Recurrence; D012307:Risk Factors; D012457:Salicylamides / Q000378:metabolism
C493593:DRD3 protein, human; D015259:Dopamine Agents; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C100958:desmethoxyfallypride; D007980:Levodopa; D004298:Dopamine