The capacity to inhibit prepotent responses is a major contributor to an individual’s vulnerability to addiction because it modulates the ability to avoid inappropriate behaviours.120,121 Such a conceptual inhibition system involves a widely distributed and more complex prefrontal cortex–subcortical circuitry. Positron emission tomography studies have uncovered substantial reductions of D2 receptor availability in the striatum in individuals with addiction that persist for months after protracted detoxification, which have also been observed in preclinical studies in rodents and non-human primates with repeated drug exposure.122 These low levels of striatal D2 receptors have been associated with decreases in baseline glucose metabolism (ie, a marker of brain function) in the prefrontal cortex (including dorsolateral prefrontal cortex, anterior cingulate gyrus, and medial orbitofrontal cortex),35,123,124 impulsivity in methamphetamine abusers,125 and compulsive cocaine administration in rodents.15 Consistent with this hypothesis, the converse is also possible. Methamphetamine-dependent individuals with striatal D2 receptor availability within the normal range had better treatment outcomes, potentially reflecting a greater ability to acquire new reward-related behaviours and the pursuit of healthy goals.126
