title: Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users.
abstract: BACKGROUND
  Dopamine D2/D3 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 D2/D3 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 [18F]fallypride.
  
  
  RESULTS
  The methamphetamine users displayed significantly lower striatal D2/D3 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 D2/D3 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 D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ballard
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Dean
authors.affiliation: VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.|Department of Physics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America.|VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.|Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000378:metabolism; D056344:Executive Function / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D008694:Methamphetamine