Deep brain stimulation of the subthalamic nucleus increases premature responding in a rat gambling task
Identifieur interne : 001077 ( Main/Exploration ); précédent : 001076; suivant : 001078Deep brain stimulation of the subthalamic nucleus increases premature responding in a rat gambling task
Auteurs : Lily R. Aleksandrova [Canada] ; Meaghan C. Creed [Canada] ; Paul J. Fletcher [Canada] ; Daniela S. S. Lobo [Canada] ; Clement Hamani [Canada] ; José N. Nobrega [Canada]Source :
- Behavioural brain research [ 0166-4328 ] ; 2013.
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- Pascal (Inist)
English descriptors
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Abstract
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n = 24) or sham surgery (n = 24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions.
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Aleksandrova</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Pharmacology and Toxicology, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Behavioural Neurobiology Laboratory and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation></author><author><name sortKey="Creed, Meaghan C" sort="Creed, Meaghan C" uniqKey="Creed M" first="Meaghan C." last="Creed">Meaghan C. Creed</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Pharmacology and Toxicology, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Behavioural Neurobiology Laboratory and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation></author><author><name sortKey="Fletcher, Paul J" sort="Fletcher, Paul J" uniqKey="Fletcher P" first="Paul J." last="Fletcher">Paul J. Fletcher</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Psychiatry, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Psychology, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Biopsychology Research Section and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation></author><author><name sortKey="Lobo, Daniela S S" sort="Lobo, Daniela S S" uniqKey="Lobo D" first="Daniela S. S." last="Lobo">Daniela S. S. Lobo</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Psychiatry, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Neurogenetics Research Section, Neuroscience Department, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Problem Gambling Service, Addictions Program, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation></author><author><name sortKey="Hamani, Clement" sort="Hamani, Clement" uniqKey="Hamani C" first="Clement" last="Hamani">Clement Hamani</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Behavioural Neurobiology Laboratory and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Division of Neurosurgery, Toronto Western Hospital</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation></author><author><name sortKey="Nobrega, Jose N" sort="Nobrega, Jose N" uniqKey="Nobrega J" first="José N." last="Nobrega">José N. Nobrega</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Pharmacology and Toxicology, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Psychiatry, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Psychology, University of Toronto</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Behavioural Neurobiology Laboratory and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health</s1><s2>Toronto, ON</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto, ON</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Behavioural brain research</title><title level="j" type="abbreviated">Behav. brain res.</title><idno type="ISSN">0166-4328</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Behavioural brain research</title><title level="j" type="abbreviated">Behav. brain res.</title><idno type="ISSN">0166-4328</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Deep brain stimulation</term><term>Gambling game</term><term>High frequency</term><term>Impulsivity</term><term>Parkinson disease</term><term>Premature</term><term>Rat</term><term>Subthalamic nucleus</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Noyau sousthalamique</term><term>Prématuré</term><term>Jeu hasard</term><term>Haute fréquence</term><term>Impulsivité</term><term>Maladie de Parkinson</term><term>Rat</term><term>Animal</term><term>Stimulation cérébrale profonde</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option for the motor symptoms of Parkinson's disease (PD). However, several recent studies have found an association between STN-DBS and increased impulsivity. Currently, it is not clear whether the observed increase in impulsivity results from STN-DBS per se, or whether it involves an interaction with the underlying PD neuropathology and/or intake of dopaminergic drugs. We investigated the effects of STN-DBS on performance of intact rats on two tasks measuring impulsive responding: a novel rat gambling task (rGT) and a differential reinforcement of low rate responding (DRL20s) schedule. Following initial behavioural training, animals received electrode implantation into the STN (n = 24) or sham surgery (n = 24), and were re-tested on their assigned behavioural task, with or without STN-DBS. Bilateral STN-DBS administered for two hours immediately prior to testing, had no effects on rGT choice behaviour or on DRL response inhibition (p>0.05). However, STN-DBS significantly increased premature responding in the rGT task (p=0.0004), an effect that took several sessions to develop and persisted in subsequent trials when no stimulation was given. Consistent with the notion of distinct facets of impulsivity with unique neurochemical underpinnings, we observed differential effects of STN-DBS in the two tasks employed. These results suggest that STN-DBS in the absence of parkinsonism may not lead to a general loss of inhibitory control, but may instead affect impulsivity under specific conditions.</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="Aleksandrova, Lily R" sort="Aleksandrova, Lily R" uniqKey="Aleksandrova L" first="Lily R." last="Aleksandrova">Lily R. Aleksandrova</name></region><name sortKey="Aleksandrova, Lily R" sort="Aleksandrova, Lily R" uniqKey="Aleksandrova L" first="Lily R." last="Aleksandrova">Lily R. Aleksandrova</name><name sortKey="Creed, Meaghan C" sort="Creed, Meaghan C" uniqKey="Creed M" first="Meaghan C." last="Creed">Meaghan C. Creed</name><name sortKey="Creed, Meaghan C" sort="Creed, Meaghan C" uniqKey="Creed M" first="Meaghan C." last="Creed">Meaghan C. Creed</name><name sortKey="Fletcher, Paul J" sort="Fletcher, Paul J" uniqKey="Fletcher P" first="Paul J." last="Fletcher">Paul J. Fletcher</name><name sortKey="Fletcher, Paul J" sort="Fletcher, Paul J" uniqKey="Fletcher P" first="Paul J." last="Fletcher">Paul J. Fletcher</name><name sortKey="Fletcher, Paul J" sort="Fletcher, Paul J" uniqKey="Fletcher P" first="Paul J." last="Fletcher">Paul J. Fletcher</name><name sortKey="Hamani, Clement" sort="Hamani, Clement" uniqKey="Hamani C" first="Clement" last="Hamani">Clement Hamani</name><name sortKey="Hamani, Clement" sort="Hamani, Clement" uniqKey="Hamani C" first="Clement" last="Hamani">Clement Hamani</name><name sortKey="Lobo, Daniela S S" sort="Lobo, Daniela S S" uniqKey="Lobo D" first="Daniela S. S." last="Lobo">Daniela S. S. Lobo</name><name sortKey="Lobo, Daniela S S" sort="Lobo, Daniela S S" uniqKey="Lobo D" first="Daniela S. S." last="Lobo">Daniela S. S. Lobo</name><name sortKey="Lobo, Daniela S S" sort="Lobo, Daniela S S" uniqKey="Lobo D" first="Daniela S. S." last="Lobo">Daniela S. S. Lobo</name><name sortKey="Nobrega, Jose N" sort="Nobrega, Jose N" uniqKey="Nobrega J" first="José N." last="Nobrega">José N. Nobrega</name><name sortKey="Nobrega, Jose N" sort="Nobrega, Jose N" uniqKey="Nobrega J" first="José N." last="Nobrega">José N. Nobrega</name><name sortKey="Nobrega, Jose N" sort="Nobrega, Jose N" uniqKey="Nobrega J" first="José N." last="Nobrega">José N. Nobrega</name><name sortKey="Nobrega, Jose N" sort="Nobrega, Jose N" uniqKey="Nobrega J" first="José N." last="Nobrega">José N. Nobrega</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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