Striatal Dopamine D(2)/D(3) Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users

BACKGROUND: Dopamine D(2)/D(3) receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D(2)/D(3) receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence. METHODS: Methamphetamine users and non-user controls (n = 18 per group) completed the Wisconsin Card Sorting Test and positron emission tomography with [(18)F]fallypride. RESULTS: The methamphetamine users displayed significantly lower striatal D(2)/D(3) receptor availability on average than controls after controlling for age and education (p = 0.008), but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622). The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D(2)/D(3) receptor availability among controls (r = -0.588, p = 0.010), but not methamphetamine users (r = 0.281, p = 0.258), and the group-wise interaction was significant (p = 0.030). CONCLUSIONS: These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D(2)/D(3) receptors in healthy controls, and that in stimulant abusers, who have lower D(2)/D(3) receptor availability, compensation can effectively maintain other executive functions, which are associated with D(2)/D(3) receptor signaling in controls.