The fundamental role of the PFC in addiction is evidenced by the increased recognition that impairments in executive function may increase the vulnerability for a substance-use disorder. Thus, it is possible that in some addicted subjects the underlying vulnerability to drugs was triggered by impairments in PFC function and that subsequent repeated drug use led to decreases in striatal D2R. Evidence for this comes from a study of subjects at high risk for alcoholism: These subjects, who were not alcoholics but had a family history of alcoholism, exhibited a higher than normal striatal D2R availability that was associated with normal metabolism in the orbitofrontal cortex, ACC, and dorsolateral PFC (34). We interpreted this to suggest that the upregulation of striatal D2R allowed these high-risk individuals to maintain adequate prefrontal function, which protected them against alcohol abuse.
