Dopamine Agonists Diminish Value Sensitivity of the Orbitofrontal Cortex: A Trigger for Pathological Gambling in Parkinson’s Disease?
Identifieur interne : 002010 ( Main/Merge ); précédent : 002009; suivant : 002011Dopamine Agonists Diminish Value Sensitivity of the Orbitofrontal Cortex: A Trigger for Pathological Gambling in Parkinson’s Disease?
Auteurs : Thilo Van Eimeren [Canada] ; Bénédicte Ballanger [Canada] ; Giovanna Pellecchia [Canada] ; Janis M. Miyasaki [Canada] ; Anthony E. Lang [Canada] ; Antonio P. Strafella [Canada]Source :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [ 0893-133X ] ; 2009.
English descriptors
- KwdEn :
- Benzothiazoles (pharmacology), Benzothiazoles (therapeutic use), Dopamine Agonists (pharmacology), Dopamine Agonists (therapeutic use), Frontal Lobe (drug effects), Frontal Lobe (physiopathology), Gambling (psychology), Humans, Levodopa (pharmacology), Levodopa (therapeutic use), Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease (complications), Parkinson Disease (drug therapy), Parkinson Disease (physiopathology), Parkinson Disease (psychology), Psychomotor Performance (drug effects), Psychomotor Performance (physiology), Reward, Risk-Taking.
- MESH :
- chemical , pharmacology : Benzothiazoles, Dopamine Agonists, Levodopa.
- chemical , therapeutic use : Benzothiazoles, Dopamine Agonists, Levodopa.
- complications : Parkinson Disease.
- drug effects : Frontal Lobe, Psychomotor Performance.
- drug therapy : Parkinson Disease.
- physiology : Psychomotor Performance.
- physiopathology : Frontal Lobe, Parkinson Disease.
- psychology : Gambling, Parkinson Disease.
- Humans, Magnetic Resonance Imaging, Male, Middle Aged, Reward, Risk-Taking.
Abstract
The neurobehavioral underpinnings of pathological gambling are not well understood. Insight might be gained by understanding pharmacological effects on the reward system in patients with Parkinson’s disease (PD). Treatment with dopamine agonists (DAs) has been associated with pathological gambling in PD patients. However, how DAs are involved in the development of this form of addiction is unknown. We tested the hypothesis that tonic stimulation of dopamine receptors specifically desensitizes the dopaminergic reward system by preventing decreases in dopaminergic transmission that occurs with negative feedback. Using functional magnetic resonance imaging, we studied PD patients during three sessions of a probabilistic reward task in random order: off medication, after levodopa (LD) treatment, and after an equivalent dose of DA (pramipexole). For each trial, a reward prediction error value was computed using outcome, stake, and probability. Pramipexole specifically changed activity of the orbitofrontal cortex (OFC) in two ways that were both associated with increased risk taking in an out-of-magnet task. Outcome-induced activations were generally higher with pramipexole compared with LD or off medication. In addition, only pramipexole greatly diminished trial-by-trial correlation with reward prediction error values. Further analysis yielded that this resulted mainly from impaired deactivation in trials with negative errors in reward prediction. We propose that DAs prevent pauses in dopamine transmission and thereby impair the negative reinforcing effect of losing. Our findings raise the question of whether pathological gambling may in part stem from an impaired capacity of the OFC to guide behavior when facing negative consequences.
Url:
DOI: 10.1038/sj.npp.npp2009124
PubMed: 19741594
PubMed Central: 2972251
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PMC:2972251Le document en format XML
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T:dopamine:agonists:diminish</idno><idno type="wicri:Area/Main/Merge">002010</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dopamine Agonists Diminish Value Sensitivity of the Orbitofrontal Cortex: A Trigger for Pathological Gambling in Parkinson’s Disease?</title><author><name sortKey="Van Eimeren, Thilo" sort="Van Eimeren, Thilo" uniqKey="Van Eimeren T" first="Thilo" last="Van Eimeren">Thilo Van Eimeren</name><affiliation wicri:level="4"><nlm:aff id="A1"> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON</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"> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON</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"> CAMH-PET Centre, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> CAMH-PET Centre, University of Toronto, Toronto, ON</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="Ballanger, Benedicte" sort="Ballanger, Benedicte" uniqKey="Ballanger B" first="Bénédicte" last="Ballanger">Bénédicte Ballanger</name><affiliation wicri:level="4"><nlm:aff id="A1"> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON</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"> CAMH-PET Centre, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> CAMH-PET Centre, University of Toronto, Toronto, ON</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="A1"> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON</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"> CAMH-PET Centre, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> CAMH-PET Centre, University of Toronto, Toronto, ON</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="A2"> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON</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="A2"> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON</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"> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Toronto, ON</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"> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON</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"> CAMH-PET Centre, University of Toronto, Toronto, ON, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> CAMH-PET Centre, University of Toronto, Toronto, ON</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">Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology</title><idno type="ISSN">0893-133X</idno><idno type="eISSN">1740-634X</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Benzothiazoles (pharmacology)</term><term>Benzothiazoles (therapeutic use)</term><term>Dopamine Agonists (pharmacology)</term><term>Dopamine Agonists (therapeutic use)</term><term>Frontal Lobe (drug effects)</term><term>Frontal Lobe (physiopathology)</term><term>Gambling (psychology)</term><term>Humans</term><term>Levodopa (pharmacology)</term><term>Levodopa (therapeutic use)</term><term>Magnetic Resonance Imaging</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (physiopathology)</term><term>Parkinson Disease (psychology)</term><term>Psychomotor Performance (drug effects)</term><term>Psychomotor Performance (physiology)</term><term>Reward</term><term>Risk-Taking</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Benzothiazoles</term><term>Dopamine Agonists</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Benzothiazoles</term><term>Dopamine Agonists</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Frontal Lobe</term><term>Psychomotor Performance</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Psychomotor Performance</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Frontal Lobe</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Gambling</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Magnetic Resonance Imaging</term><term>Male</term><term>Middle Aged</term><term>Reward</term><term>Risk-Taking</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The neurobehavioral underpinnings of pathological gambling are not well understood. Insight might be gained by understanding pharmacological effects on the reward system in patients with Parkinson’s disease (PD). Treatment with dopamine agonists (DAs) has been associated with pathological gambling in PD patients. However, how DAs are involved in the development of this form of addiction is unknown. We tested the hypothesis that tonic stimulation of dopamine receptors specifically desensitizes the dopaminergic reward system by preventing decreases in dopaminergic transmission that occurs with negative feedback. Using functional magnetic resonance imaging, we studied PD patients during three sessions of a probabilistic reward task in random order: off medication, after levodopa (LD) treatment, and after an equivalent dose of DA (pramipexole). For each trial, a reward prediction error value was computed using outcome, stake, and probability. Pramipexole specifically changed activity of the orbitofrontal cortex (OFC) in two ways that were both associated with increased risk taking in an out-of-magnet task. Outcome-induced activations were generally higher with pramipexole compared with LD or off medication. In addition, only pramipexole greatly diminished trial-by-trial correlation with reward prediction error values. Further analysis yielded that this resulted mainly from impaired deactivation in trials with negative errors in reward prediction. We propose that DAs prevent pauses in dopamine transmission and thereby impair the negative reinforcing effect of losing. Our findings raise the question of whether pathological gambling may in part stem from an impaired capacity of the OFC to guide behavior when facing negative consequences.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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