title: D3 dopamine receptor-preferring [11C]PHNO PET imaging in Parkinson patients with dyskinesia.
abstract: OBJECTIVE
  To investigate whether levodopa-induced dyskinesias (LID) are associated with D3 overexpression in levodopa-treated humans with Parkinson disease (PD).
  
  
  METHODS
  In this case-control study, we used PET with the D3-preferring radioligand [(11)C]-(+)-PHNO to estimate D2/3 receptor binding in patients with levodopa-treated PD with LID (n = 12) and without LID (n = 12), and healthy control subjects matched for age, sex, education, and mental status (n = 18).
  
  
  RESULTS
  Compared to nondyskinetic patients, those with LID showed heightened [(11)C]-(+)-PHNO binding in the D3-rich globus pallidus. Both PD groups also showed higher binding than controls in the sensorimotor division of the striatum. In contrast, D2/3 binding in the ventral striatum was lower in patients with LID than without, possibly reflecting higher dopamine levels.
  
  
  CONCLUSIONS
  Dopaminergic abnormalities contributing to LID may include elevated D2/3 binding in globus pallidus, perhaps reflecting D3 receptor upregulation. The findings support therapeutic strategies that target and diminish activity at D3 to prevent LID.
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Doris E
authors.initials: DE
authors.lastname: Payer
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Guttman
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Adams
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furukawa
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: From the Addictions Program (D.E.P., I.B.), the Research Imaging Centre (D.E.P., S.J.K., J.T., P.R., S.H., A.A.W., I.B.), and the Human Brain Laboratory (M.G., S.J.K., Y.F.), Centre for Addiction and Mental Health, Toronto; Campbell Family Mental Health Research Institute (S.J.K., J.T., P.R., S.H., A.A.W., I.B.), Toronto; the Departments of Psychiatry (D.E.P., S.J.K., J.T., A.A.W., I.B.) and Pharmacology (S.J.K.), University of Toronto; and the Centre for Movement Disorders (M.G., J.R.A.), Markham, Canada. isabelle.boileau@camh.ca.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
mesh_terms: D000368:Aged; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D015259:Dopamine Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000000981:diagnostic imaging* / Q000209:etiology; D005260:Female; D005917:Globus Pallidus / Q000000981:diagnostic imaging*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy; D049268:Positron-Emission Tomography / Q000379:methods*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D015854:Up-Regulation; D066328:Ventral Striatum / Q000000981:diagnostic imaging
chemical_list: D002250:Carbon Radioisotopes; D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D007980:Levodopa