From the animal literature, it was clear that a variation in the CNR1 gene associated with increased levels of CB1 receptors in the PFC might alter the acquisition or expression of incentive salience for alcohol. To test this functional hypothesis, a neuroimaging paradigm examined the activation of mesocorticolimbic structures during exposure to the taste of an alcoholic beverage. The findings suggest that the C allele of rs2023239 is associated with greater activation of the NAcc, OFC, VTA, and VMPFC during exposure to alcohol vs either rest or control (ie, juice) cues. Not only do individuals with the CT genotype demonstrate greater activation in these key structures, but this activation (ie, the alcohol vs control contrast) is also strongly associated with alcohol use disorder and craving measures in individuals with the CT genotype. The findings from the neuroimaging study suggest that rs2023239 may be associated with changes in the mesocorticolimbic neurocircuitry, which, in turn, may mediate a change in the incentive salience of alcohol and the risk of an alcohol use disorder.
