Journal
ARCHIVES OF GENERAL PSYCHIATRY
Volume 65, Issue 7, Pages 841-850Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/archpsyc.65.7.841
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Funding
- NCI NIH HHS [P01 CA089392] Funding Source: Medline
- NIAAA NIH HHS [R01 AA012238-05, R01 AA012238-06A2, AA012238, R01 AA012238-04, R01 AA012238-09, R29 AA012238, R01 AA012238-08, R01 AA012238-07, R28 AA012725, R01 AA012238, R01 AA012238-03, R01 AA012238-10, R01 AA012238-11] Funding Source: Medline
- NIBIB NIH HHS [R01 EB006841, R01 EB020407] Funding Source: Medline
- NIDA NIH HHS [R01 DA014369-04, R01 DA014369-05, R01 DA014369-03, F31 DA021496, DA14369, R01 DA040487, R01 DA014369-01, R01 DA014369, R01 DA014369-02] Funding Source: Medline
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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 neuro-circuitry that is involved in the attribution of incentive salience after repeated exposure to alcohol.
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