Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease.
Identifieur interne : 002B08 ( PubMed/Curation ); précédent : 002B07; suivant : 002B09Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease.
Auteurs : Naomi P. Visanji [Canada] ; Jordi Gomez-Ramirez ; Tom H. Johnston ; Donna Pires ; Valerie Voon ; Jonathan M. Brotchie ; Susan H. FoxSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2006.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Amantadine (therapeutic use), Animals, Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Apomorphine (adverse effects), Behavior, Animal (drug effects), Behavior, Animal (physiology), Callithrix, Disability Evaluation, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, Dyskinesia, Drug-Induced (drug therapy), Dyskinesia, Drug-Induced (etiology), Dyskinesia, Drug-Induced (physiopathology), Female, Grooming (drug effects), Grooming (physiology), Hallucinations (drug therapy), Hallucinations (etiology), Levodopa (adverse effects), Parkinsonian Disorders (chemically induced), Parkinsonian Disorders (drug therapy), Parkinsonian Disorders (physiopathology), Psychomotor Agitation (drug therapy), Psychomotor Agitation (etiology), Psychotic Disorders (drug therapy), Psychotic Disorders (etiology), Psychotic Disorders (physiopathology), Statistics, Nonparametric, Stereotyped Behavior (drug effects), Stereotyped Behavior (physiology).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Apomorphine, Levodopa.
- chemical , therapeutic use : Amantadine, Antiparkinson Agents.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinsonian Disorders.
- drug effects : Behavior, Animal, Grooming, Stereotyped Behavior.
- drug therapy : Dyskinesia, Drug-Induced, Hallucinations, Parkinsonian Disorders, Psychomotor Agitation, Psychotic Disorders.
- etiology : Dyskinesia, Drug-Induced, Hallucinations, Psychomotor Agitation, Psychotic Disorders.
- physiology : Behavior, Animal, Grooming, Stereotyped Behavior.
- physiopathology : Dyskinesia, Drug-Induced, Parkinsonian Disorders, Psychotic Disorders.
- Animals, Callithrix, Disability Evaluation, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, Female, Statistics, Nonparametric.
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.
DOI: 10.1002/mds.21073
PubMed: 16960862
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Johnston</name></author><author><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name></author><author><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name></author><author><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. 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Johnston</name></author><author><name sortKey="Pires, Donna" sort="Pires, Donna" uniqKey="Pires D" first="Donna" last="Pires">Donna Pires</name></author><author><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name></author><author><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Amantadine (therapeutic use)</term><term>Animals</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Apomorphine (adverse effects)</term><term>Behavior, Animal (drug effects)</term><term>Behavior, Animal (physiology)</term><term>Callithrix</term><term>Disability Evaluation</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Drug Interactions</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Dyskinesia, Drug-Induced (physiopathology)</term><term>Female</term><term>Grooming (drug effects)</term><term>Grooming (physiology)</term><term>Hallucinations (drug therapy)</term><term>Hallucinations (etiology)</term><term>Levodopa (adverse effects)</term><term>Parkinsonian Disorders (chemically induced)</term><term>Parkinsonian Disorders (drug therapy)</term><term>Parkinsonian Disorders (physiopathology)</term><term>Psychomotor Agitation (drug therapy)</term><term>Psychomotor Agitation (etiology)</term><term>Psychotic Disorders (drug therapy)</term><term>Psychotic Disorders (etiology)</term><term>Psychotic Disorders (physiopathology)</term><term>Statistics, Nonparametric</term><term>Stereotyped Behavior (drug effects)</term><term>Stereotyped Behavior (physiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Apomorphine</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Amantadine</term><term>Antiparkinson Agents</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Behavior, Animal</term><term>Grooming</term><term>Stereotyped Behavior</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Hallucinations</term><term>Parkinsonian Disorders</term><term>Psychomotor Agitation</term><term>Psychotic Disorders</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Hallucinations</term><term>Psychomotor Agitation</term><term>Psychotic Disorders</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Behavior, Animal</term><term>Grooming</term><term>Stereotyped Behavior</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinsonian Disorders</term><term>Psychotic Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Callithrix</term><term>Disability Evaluation</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Drug Interactions</term><term>Female</term><term>Statistics, Nonparametric</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><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">16960862</PMID><DateCreated><Year>2006</Year><Month>12</Month><Day>05</Day></DateCreated><DateCompleted><Year>2007</Year><Month>02</Month><Day>20</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>21</Volume><Issue>11</Issue><PubDate><Year>2006</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>1879-91</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Visanji</LastName><ForeName>Naomi P</ForeName><Initials>NP</Initials><AffiliationInfo><Affiliation>Toronto Western Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gomez-Ramirez</LastName><ForeName>Jordi</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Johnston</LastName><ForeName>Tom H</ForeName><Initials>TH</Initials></Author><Author ValidYN="Y"><LastName>Pires</LastName><ForeName>Donna</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Voon</LastName><ForeName>Valerie</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Brotchie</LastName><ForeName>Jonathan M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Fox</LastName><ForeName>Susan H</ForeName><Initials>SH</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>9P21XSP91P</RegistryNumber><NameOfSubstance UI="D015632">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</NameOfSubstance></Chemical><Chemical><RegistryNumber>BF4C9Z1J53</RegistryNumber><NameOfSubstance UI="D000547">Amantadine</NameOfSubstance></Chemical><Chemical><RegistryNumber>N21FAR7B4S</RegistryNumber><NameOfSubstance UI="D001058">Apomorphine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D015632">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000547">Amantadine</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000818">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000978">Antiparkinson Agents</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000627">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001058">Apomorphine</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001522">Behavior, Animal</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000502">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002144">Callithrix</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004185">Disability Evaluation</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004195">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004305">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004347">Drug Interactions</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004409">Dyskinesia, Drug-Induced</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000188">drug therapy</QualifierName><QualifierName MajorTopicYN="N" UI="Q000209">etiology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006120">Grooming</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000502">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006212">Hallucinations</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000188">drug therapy</QualifierName><QualifierName MajorTopicYN="N" UI="Q000209">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007980">Levodopa</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000009">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D020734">Parkinsonian Disorders</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000139">chemically induced</QualifierName><QualifierName MajorTopicYN="N" UI="Q000188">drug therapy</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011595">Psychomotor Agitation</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000188">drug therapy</QualifierName><QualifierName MajorTopicYN="N" UI="Q000209">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011618">Psychotic Disorders</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000188">drug therapy</QualifierName><QualifierName MajorTopicYN="N" UI="Q000209">etiology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D018709">Statistics, Nonparametric</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013239">Stereotyped Behavior</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000502">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>9</Month><Day>9</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>2</Month><Day>21</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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