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Sex Differences in Striatal Dopamine Release in Young Adults After Oral Alcohol Challenge: A Positron Emission Tomography Imaging Study With [11C]Raclopride
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Background We used a positron emission tomography paradigm with the D2/3 radiotracer [¹¹C]raclopride and an alcohol challenge to examine the magnitude of alcohol-induced dopamine release and compare it between young men and women.Methods Twenty-one nonalcohol-dependent young social drinkers completed two positron emission tomography scans on separate days following ingestion of a juice mix containing either ethanol (.75 mg/kg body water) or trace ethanol only. The extent of dopamine released after alcohol was estimated by the percentage difference in [¹¹C]raclopride binding potential (ΔBP(ND)) between days.Results Alcohol administration significantly displaced [¹¹C]raclopride in all striatal subregions, indicating dopamine release, with the largest effect observed in the ventral striatum. Linear mixed model analysis across all striatal subregions of regional ΔBP(ND) with region of interest as repeated measure showed a highly significant effect of sex (p < .001). Ventrostriatal dopamine release in men, but not in women, showed a significant positive correlation to alcohol-induced measures of subjective activation. Furthermore, we found a significant negative correlation between the frequency of maximum alcohol consumption per 24 hours and ventrostriatal ΔBP(ND) (r = .739, p = .009) in men.Conclusions This study provides definitive evidence that oral alcohol induces dopamine release in nonalcoholic human subjects and shows sex differences in the magnitude of this effect. The ability of alcohol to stimulate dopamine release may contribute to its rewarding effects and, thereby, to its abuse liability in humans. Our report further suggests several biological mechanisms that may mediate the difference in vulnerability for alcoholism between men and women.
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“In humans, consistent with animal studies, oral doses of alcohol increased extracellular dopamine concentrations during intoxication in healthy volunteers, based on positron emission tomography measures (Boileau et al., 2003;Urban et al., 2010).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Urban et al., 2010
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Metadata
- Authors
- Urban, N. B. L., Kegeles, L. S., Slifstein, M., Xu, X., Martinez, D., Sakr, E., Castillo, F., Moadel, T., O'Malley, S. S., Krystal, J. H., & Abi-Dargham, A.
- Affiliations
- New York State Psychiatric Institute (US)
- Yale University (US)
- Corresponding author
- Urban, Nina B.L.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 68
- Issue
- 8
- Pages
- 689-696
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2949533
- OpenAlex
- W2014500606
- Cited by
- 223
- References
- 57
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 18 · 2020: 34 · 2019: 12 · 2018: 15 · 2017: 15 · 2016: 13 · 2015: 11 · 2014: 22 · 2013: 11 · 2012: 8
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism
- Yale University (P50AA-012870-09)
- 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
- sex differences, dopamine release, striatum, alcohol challenge, [11C]raclopride, ventral striatum, alcohol reward, drinking frequency, young adults
- MeSH terms
- Adult, Alcohol Drinking, Carbon Radioisotopes, Corpus Striatum, Dopamine, Female, Humans, Male, Radioligand Assay, Sex Characteristics, Raclopride, Positron-Emission Tomography
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