Recently, in a positron emission tomography (PET) study of 22 smokers and 20 controls, the 118G variant was associated with reduced receptor binding availability in the bilateral amygdala, left thalamus, and left anterior cingulate cortex (Ray et al. 2011). An fMRI study showed that the 118G allele is associated with increased cue-elicited activation of mesocorticolimbic structures and that this activation is extended by a priming dose of alcohol. This activity in the striatum was correlated with drinking behavior in individuals with the 118G allele (Filbey et al. 2008; Ramchandani et al. 2011). Taken together, some results may be interpreted as a loss-of-function while others may be interpreted as a gain-of-function of the 118G receptor. These results are not mutually exclusive and it is possible that the variant causes reduction in receptor numbers but also enhanced binding. It is also possible that some results reflect the action of another SNP that is in high LD with the 118G allele in some chromosomes (haplotypes) but not in others. The exact nature of the physiological changes has yet to be elucidated.
