Document Detail

Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson's patients with medication-induced pathological gambling: a [11C] FLB-457 and PET study.
MedLine Citation:
PMID:  22766031     Owner:  NLM     Status:  MEDLINE    
Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson's disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait.
Nicola J Ray; Janis M Miyasaki; Mateusz Zurowski; Ji Hyun Ko; Sang Soo Cho; Giovanna Pellecchia; Francesca Antonelli; Sylvain Houle; Anthony E Lang; Antonio P Strafella
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-03
Journal Detail:
Title:  Neurobiology of disease     Volume:  48     ISSN:  1095-953X     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-09-28     Completed Date:  2013-04-30     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  519-25     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Dopamine / metabolism*
Dopamine Agonists / adverse effects*
Gambling / chemically induced,  metabolism,  radionuclide imaging*
Homeostasis / physiology*
Mesencephalon / radionuclide imaging*
Middle Aged
Parkinson Disease / metabolism,  psychology,  radionuclide imaging*
Positron-Emission Tomography
Pyrrolidines / diagnostic use
Radiopharmaceuticals / diagnostic use
Salicylamides / diagnostic use
Grant Support
110962//Canadian Institutes of Health Research; MOP 110962//Canadian Institutes of Health Research
Reg. No./Substance:
0/Dopamine Agonists; 0/Pyrrolidines; 0/Radiopharmaceuticals; 0/Salicylamides; 107188-66-9/FLB 457

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