Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study
Identifieur interne : 001234 ( Main/Exploration ); précédent : 001233; suivant : 001235Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study
Auteurs : Nicola J. Ray [Canada] ; Janis M. Miyasaki [Canada] ; Mateusz Zurowski [Canada] ; Ji Hyun Ko [Canada] ; Sang Soo Cho [Canada] ; Giovanna Pellecchia [Canada] ; Francesca Antonelli [Canada] ; Sylvain Houle [Canada] ; Anthony E. Lang [Canada] ; Antonio P. Strafella [Canada]Source :
- Neurobiology of disease [ 0969-9961 ] ; 2012.
English descriptors
- KwdEn :
- Dopamine (metabolism), Dopamine Agonists (adverse effects), Gambling (chemically induced), Gambling (diagnostic imaging), Gambling (metabolism), Homeostasis (physiology), Humans, Mesencephalon (diagnostic imaging), Middle Aged, Parkinson Disease (diagnostic imaging), Parkinson Disease (metabolism), Parkinson Disease (psychology), Positron-Emission Tomography, Pyrrolidines, Radiopharmaceuticals, Salicylamides.
- MESH :
- chemical , adverse effects : Dopamine Agonists.
- chemical , metabolism : Dopamine.
- chemically induced : Gambling.
- diagnostic imaging : Gambling, Mesencephalon, Parkinson Disease.
- metabolism : Gambling, Parkinson Disease.
- physiology : Homeostasis.
- psychology : Parkinson Disease.
- Humans, Middle Aged, Positron-Emission Tomography, Pyrrolidines, Radiopharmaceuticals, Salicylamides.
Abstract
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.
Url:
DOI: 10.1016/j.nbd.2012.06.021
PubMed: 22766031
PubMed Central: 3465363
Affiliations:
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Le document en format XML
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Ray</name><affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Miyasaki, Janis M" sort="Miyasaki, Janis M" uniqKey="Miyasaki J" first="Janis M." last="Miyasaki">Janis M. Miyasaki</name><affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Zurowski, Mateusz" sort="Zurowski, Mateusz" uniqKey="Zurowski M" first="Mateusz" last="Zurowski">Mateusz Zurowski</name><affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Ko, Ji Hyun" sort="Ko, Ji Hyun" uniqKey="Ko J" first="Ji Hyun" last="Ko">Ji Hyun Ko</name><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Cho, Sang Soo" sort="Cho, Sang Soo" uniqKey="Cho S" first="Sang Soo" last="Cho">Sang Soo Cho</name><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Pellecchia, Giovanna" sort="Pellecchia, Giovanna" uniqKey="Pellecchia G" first="Giovanna" last="Pellecchia">Giovanna Pellecchia</name><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Antonelli, Francesca" sort="Antonelli, Francesca" uniqKey="Antonelli F" first="Francesca" last="Antonelli">Francesca Antonelli</name><affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation wicri:level="4"><nlm:aff id="A1">Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A2">Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A3">Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="ISSN">0969-9961</idno><idno type="eISSN">1095-953X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine (metabolism)</term><term>Dopamine Agonists (adverse effects)</term><term>Gambling (chemically induced)</term><term>Gambling (diagnostic imaging)</term><term>Gambling (metabolism)</term><term>Homeostasis (physiology)</term><term>Humans</term><term>Mesencephalon (diagnostic imaging)</term><term>Middle Aged</term><term>Parkinson Disease (diagnostic imaging)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (psychology)</term><term>Positron-Emission Tomography</term><term>Pyrrolidines</term><term>Radiopharmaceuticals</term><term>Salicylamides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Dopamine Agonists</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Gambling</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Gambling</term><term>Mesencephalon</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Gambling</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Homeostasis</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Middle Aged</term><term>Positron-Emission Tomography</term><term>Pyrrolidines</term><term>Radiopharmaceuticals</term><term>Salicylamides</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">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.</p></div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Ray, Nicola J" sort="Ray, Nicola J" uniqKey="Ray N" first="Nicola J." last="Ray">Nicola J. Ray</name></region><name sortKey="Antonelli, Francesca" sort="Antonelli, Francesca" uniqKey="Antonelli F" first="Francesca" last="Antonelli">Francesca Antonelli</name><name sortKey="Antonelli, Francesca" sort="Antonelli, Francesca" uniqKey="Antonelli F" first="Francesca" last="Antonelli">Francesca Antonelli</name><name sortKey="Antonelli, Francesca" sort="Antonelli, Francesca" uniqKey="Antonelli F" first="Francesca" last="Antonelli">Francesca Antonelli</name><name sortKey="Cho, Sang Soo" sort="Cho, Sang Soo" uniqKey="Cho S" first="Sang Soo" last="Cho">Sang Soo Cho</name><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><name sortKey="Ko, Ji Hyun" sort="Ko, Ji Hyun" uniqKey="Ko J" first="Ji Hyun" last="Ko">Ji Hyun Ko</name><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><name sortKey="Miyasaki, Janis M" sort="Miyasaki, Janis M" uniqKey="Miyasaki J" first="Janis M." last="Miyasaki">Janis M. Miyasaki</name><name sortKey="Pellecchia, Giovanna" sort="Pellecchia, Giovanna" uniqKey="Pellecchia G" first="Giovanna" last="Pellecchia">Giovanna Pellecchia</name><name sortKey="Pellecchia, Giovanna" sort="Pellecchia, Giovanna" uniqKey="Pellecchia G" first="Giovanna" last="Pellecchia">Giovanna Pellecchia</name><name sortKey="Ray, Nicola J" sort="Ray, Nicola J" uniqKey="Ray N" first="Nicola J." last="Ray">Nicola J. Ray</name><name sortKey="Ray, Nicola J" sort="Ray, Nicola J" uniqKey="Ray N" first="Nicola J." last="Ray">Nicola J. Ray</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Zurowski, Mateusz" sort="Zurowski, Mateusz" uniqKey="Zurowski M" first="Mateusz" last="Zurowski">Mateusz Zurowski</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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