The Incentive Salience of Alcohol: Translating the Effects of Genetic Variant in CNR1
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CONTEXT: The gene that codes for cannabinoid receptor 1 (CNR1) represents an important target for investigations designed to elucidate individual differences in the etiology of alcohol dependence. OBJECTIVE: To achieve a better understanding of the role of the CNR1 gene in the etiology and treatment of alcohol dependence. DESIGN: The present investigation spans multiple levels of analysis, including receptor binding in postmortem brain tissue, neuroimaging, human laboratory models, and analyses of treatment outcome data. RESULTS: Findings indicate that the C allele of rs2023239 is associated with greater CB1 binding in the prefrontal cortex, greater alcohol cue-elicited brain activation in the midbrain and prefrontal cortex, greater subjective reward when consuming alcohol, and more positive outcomes after treatment with a medication that targets the mesocorticolimbic neurocircuitry. In addition, there were strong correlations between cue-elicited brain activation and alcohol consumption measures in individuals with the C allele. CONCLUSION: Individuals with the C allele may be more susceptible to changes in the mesocorticolimbic neurocircuitry that is involved in the attribution of incentive salience after repeated exposure to alcohol.
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Human studies in this area have been limited to retrospective patient reports, post mortem brain tissue methods, or cross-sectional laboratory paradigms, none of which directly measure alcohol responses in the same individuals over time.
“Human studies in this area have been limited to retrospective patient reports(23), post mortem brain tissue methods(24), or cross-sectional laboratory paradigms(2, 3, 25–29), none of which directly measure alcohol responses in the same individuals over time.”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [24]
Previous studies relying on proxy measures of brain-behavior relationships to alcohol response have not been able to address within-person changes or stabilization in alcohol response over time.
“Previous studies relying on proxy measures of brain-behavior relationships to alcohol response(2, 3, 23–29) have not been able to address within-person changes or stabilization in alcohol response over time.”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [24]
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- Authors
- Hutchison, K. E., Haughey, H., Niculescu, M., Schacht, J., Kaiser, A., Stitzel, J., Horton, W. J., & Filbey, F.
- Affiliations
- University of Colorado Boulder (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2008-07-07
- Volume
- 65
- Issue
- 7
- Pages
- 841
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2856651
- OpenAlex
- W2111593384
- Cited by
- 102
- References
- 53
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 9
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (R01AA012238, AA012238, R29AA012238, R28AA012725)
- National Institute on Drug Abuse (R01DA040487, DA-14369, R01DA014369)
- National Cancer Institute (P01CA089392)
- National Institute of Biomedical Imaging and Bioengineering (R01EB020407, R01EB006841)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alcoholism, CB1 receptor, CNR1 gene, incentive salience, alcohol cue reactivity, mesocorticolimbic circuitry, prefrontal cortex, pharmacogenetics
- MeSH terms
- Adolescent, Adult, Alcohol Drinking, Brain, Genotype, Humans, Male, Genetic Variation, Gene Expression, Genomics, Receptor, Cannabinoid, CB1
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