Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease
Identifieur interne : 001966 ( PascalFrancis/Checkpoint ); précédent : 001965; suivant : 001967Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease
Auteurs : Naomi P. Visanji [Canada] ; Jordi Gomez-Ramirez [Canada] ; Tom H. Johnston [Canada] ; Donna Pires [Canada] ; Valerie Voon [Canada] ; Jonathan M. Brotchie [Canada] ; Susan H. Fox [Canada]Source :
- Movement disorders [ 0885-3185 ] ; 2006.
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- Pascal (Inist)
English descriptors
Abstract
Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior-agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like"-and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression.
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Visanji</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Gomez Ramirez, Jordi" sort="Gomez Ramirez, Jordi" uniqKey="Gomez Ramirez J" first="Jordi" last="Gomez-Ramirez">Jordi Gomez-Ramirez</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Johnston, Tom H" sort="Johnston, Tom H" uniqKey="Johnston T" first="Tom H." last="Johnston">Tom H. Johnston</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Psychiatry, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M." last="Brotchie">Jonathan M. 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Fox</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Division of Neurology, University of Toronto</s1><s2>Toronto</s2><s3>CAN</s3><sZ>7 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></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0021714</idno><date when="2006">2006</date><idno type="stanalyst">PASCAL 07-0021714 INIST</idno><idno type="RBID">Pascal:07-0021714</idno><idno type="wicri:Area/PascalFrancis/Corpus">001917</idno><idno type="wicri:Area/PascalFrancis/Curation">001404</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">001966</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease</title><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Gomez Ramirez, Jordi" sort="Gomez Ramirez, Jordi" uniqKey="Gomez Ramirez J" first="Jordi" last="Gomez-Ramirez">Jordi Gomez-Ramirez</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Johnston, Tom H" sort="Johnston, Tom H" uniqKey="Johnston T" first="Tom H." last="Johnston">Tom H. Johnston</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Psychiatry, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M." last="Brotchie">Jonathan M. Brotchie</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H." last="Fox">Susan H. Fox</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Division of Neurology, University of Toronto</s1><s2>Toronto</s2><s3>CAN</s3><sZ>7 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></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal model</term><term>Behavior</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Primates</term><term>Psychosis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Psychose</term><term>Parkinson maladie</term><term>Comportement</term><term>Primates</term><term>Modèle animal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior-agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like"-and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>21</s2></fA05><fA06><s2>11</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease</s1></fA08><fA11 i1="01" i2="1"><s1>VISANJI (Naomi P.)</s1></fA11><fA11 i1="02" i2="1"><s1>GOMEZ-RAMIREZ (Jordi)</s1></fA11><fA11 i1="03" i2="1"><s1>JOHNSTON (Tom H.)</s1></fA11><fA11 i1="04" i2="1"><s1>PIRES (Donna)</s1></fA11><fA11 i1="05" i2="1"><s1>VOON (Valerie)</s1></fA11><fA11 i1="06" i2="1"><s1>BROTCHIE (Jonathan M.)</s1></fA11><fA11 i1="07" i2="1"><s1>FOX (Susan H.)</s1></fA11><fA14 i1="01"><s1>Toronto Western Research Institute, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Psychiatry, Toronto Western Hospital</s1><s2>Toronto</s2><s3>CAN</s3><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Division of Neurology, University of Toronto</s1><s2>Toronto</s2><s3>CAN</s3><sZ>7 aut.</sZ></fA14><fA20><s1>1879-1891</s1></fA20><fA21><s1>2006</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000158935070110</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>74 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>07-0021714</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior-agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like"-and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC02 i1="03" i2="X"><s0>002B17A03</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Système nerveux pathologie</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Psychose</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Psychosis</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Psicosis</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Parkinson disease</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Comportement</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Behavior</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Conducta</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Primates</s0><s2>NS</s2><s5>10</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Primates</s0><s2>NS</s2><s5>10</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Primates</s0><s2>NS</s2><s5>10</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Modèle animal</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Animal model</s0><s5>11</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Modelo animal</s0><s5>11</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Encéphale pathologie</s0><s5>37</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0><s5>40</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>40</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>40</s5></fC07><fN21><s1>010</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><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"><noRegion><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name></noRegion><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M." last="Brotchie">Jonathan M. Brotchie</name><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H." last="Fox">Susan H. Fox</name><name sortKey="Gomez Ramirez, Jordi" sort="Gomez Ramirez, Jordi" uniqKey="Gomez Ramirez J" first="Jordi" last="Gomez-Ramirez">Jordi Gomez-Ramirez</name><name sortKey="Johnston, Tom H" sort="Johnston, Tom H" uniqKey="Johnston T" first="Tom H." last="Johnston">Tom H. Johnston</name><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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