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Original Article
July 7, 2008

The Incentive Salience of Alcohol: Translating the Effects of Genetic Variant in CNR1

Author Affiliations

Author Affiliations: Department of Psychology (Drs Hutchison, Haughey, Niculescu, Kaiser, and Filbey and Mr Schacht) and Institute of Behavioral Genetics (Dr Stitzel and Mr Horton), University of Colorado at Boulder. Drs Hutchison and Filbey are now with The MIND, Albuquerque, New Mexico.

Arch Gen Psychiatry. 2008;65(7):841-850. doi:10.1001/archpsyc.65.7.841

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.