Doris E Payer1, Mark Guttman1, Stephen J Kish1, Junchao Tong1, John R Adams1, Pablo Rusjan1, Sylvain Houle1, Yoshiaki Furukawa1, Alan A Wilson1, Isabelle Boileau2. 1. 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. 2. 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.
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.
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.
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