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Correlation of Alcohol Craving With Striatal Dopamine Synthesis Capacity and D 2/3 Receptor Availability: A Combined [ 18 F]DOPA and [ 18 F]DMFP PET Study in Detoxified Alcoholic Patients
Abstract
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. METHOD: 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.
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“In alcohol dependence, Hietala et al (Hietala et al., 1994) showed a decrease in D2 receptor availability in the striatum and this has now been replicated in additional studies (Heinz et al., 2005; Heinz et al., 2004; Martinez et al., 2005; Volkow et al., 1996; Volkow et al., 2002b; Volkow et al., 2007b), although some groups report a lack of a difference”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Heinz et al., 2005
In the citing paper
“In alcohol dependence, imaging studies show a reduction in VMAT2 compared to controls (Gilman et al., 1998) although not of [18F]DOPA uptake (Heinz et al., 2005; Tiihonen et al., 1998).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Heinz et al., 2005
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Metadata
- Authors
- Heinz, A., Siessmeier, T., Wrase, J., Buchholz, H. G., Gründer, G., Kumakura, Y., Cumming, P., Schreckenberger, M., Smolka, M. N., Rösch, F., Mann, K., & Bartenstein, P.
- Affiliations
- Central Institute of Mental Health (DE)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2005-08-01
- Volume
- 162
- Issue
- 8
- Pages
- 1515-1520
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2121548568
- Cited by
- 285
- References
- 30
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 9 · 2020: 31 · 2019: 14 · 2018: 15 · 2017: 13 · 2016: 15 · 2015: 11 · 2014: 22 · 2013: 13 · 2012: 24
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- alcohol craving, alcoholism, dopamine synthesis capacity, dopamine D2/D3 receptors, striatum, putamen, alcohol relapse, alcohol abstinence, dopamine signaling, alcohol consumption
- MeSH terms
- Adult, Alcoholism, Blood-Brain Barrier, Corpus Striatum, Dopamine, Fluorine Radioisotopes, Follow-Up Studies, Humans, Levodopa, Male, Middle Aged, Recurrence, Risk Factors, Salicylamides, Dopamine Agents, Behavior, Addictive, Receptors, Dopamine D2, Positron-Emission Tomography, Receptors, Dopamine D3
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