Relevance of the MPTP primate model in the study of dyskinesia priming mechanisms

Pierre J. Blanchet; Frédéric Calon; Marc Morissette; Abdallah Hadj Tahar; Nancy Bélanger; Pershia Samadi; Richard Grondin; Laurent Grégoire; Leonard Meltzer; Thérèse Di Paolo; Paul J. Bédard

doi:10.1016/j.parkreldis.2004.02.011

Relevance of the MPTP primate model in the study of dyskinesia priming mechanisms

Pierre J. Blanchet, Frédéric Calon, Marc Morissette, Abdallah Hadj Tahar, Nancy Bélanger, Pershia Samadi, Richard Grondin, Laurent Grégoire, Leonard Meltzer, Thérèse Di Paolo, Paul J. Bédard

Research output: Contribution to journal › Conference article › peer-review

60 Scopus citations

Abstract

For nearly 20 years, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model has allowed great strides to be made in our understanding of the maladaptive changes underlying the levodopa-related motor response complications occurring in most parkinsonian patients. Studies indicate that sustained dopamine D2 receptor occupancy can prevent and reverse existing dyskinesias. Recent experiments in levodopa-treated MPTP animals, co-administered either a threshold dose of cabergoline or a glutamate NMDA NR2B-selective antagonist (CI-1041), have afforded protection against dyskinesia, perhaps through presynaptic inhibition of glutamate release and blockade of supersensitive postsynaptic NMDA receptors in the striatum, respectively. Some of the biochemical events that have correlated with dyskinesias, namely upregulated GABA_A receptors in the internal pallidum, rise in pre-proenkephalin-A gene expression in the striatum, and upregulated striatal glutamate ionotropic receptors and adenosine A_2a receptors, may be counteracted by these preventive strategies.

Original language	English
Pages (from-to)	297-304
Number of pages	8
Journal	Parkinsonism and Related Disorders
Volume	10
Issue number	5
DOIs	https://doi.org/10.1016/j.parkreldis.2004.02.011
State	Published - Jul 2004
Event	Striatal Plasticity in Health and Disease - Stockholm, Sweden Duration: Nov 28 2003 → Nov 29 2003

Bibliographical note

Funding Information:
This work was supported by grants from the Canadian Institutes for Health Research (CIHR) to P. Bedard and T. Di Paolo. F. Calon was the recipient of a health professional studentship from Novartis in partnership with CIHR and the Quebec Health Research Fund (FRSQ). The Authors are also grateful to Dr Ali H. Rajput, Royal University Hospital, University of Saskatchewan, for providing human brain tissue. Mrs M.-T. Parent kindly provided assistance in the preparation of the manuscript.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dyskinesia
Parkinson's disease

ASJC Scopus subject areas

Neurology
Geriatrics and Gerontology
Clinical Neurology

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10.1016/j.parkreldis.2004.02.011

Cite this

@article{bf889fb61b944634a2f8633db37572d3,

title = "Relevance of the MPTP primate model in the study of dyskinesia priming mechanisms",

abstract = "For nearly 20 years, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model has allowed great strides to be made in our understanding of the maladaptive changes underlying the levodopa-related motor response complications occurring in most parkinsonian patients. Studies indicate that sustained dopamine D2 receptor occupancy can prevent and reverse existing dyskinesias. Recent experiments in levodopa-treated MPTP animals, co-administered either a threshold dose of cabergoline or a glutamate NMDA NR2B-selective antagonist (CI-1041), have afforded protection against dyskinesia, perhaps through presynaptic inhibition of glutamate release and blockade of supersensitive postsynaptic NMDA receptors in the striatum, respectively. Some of the biochemical events that have correlated with dyskinesias, namely upregulated GABAA receptors in the internal pallidum, rise in pre-proenkephalin-A gene expression in the striatum, and upregulated striatal glutamate ionotropic receptors and adenosine A2a receptors, may be counteracted by these preventive strategies.",

keywords = "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dyskinesia, Parkinson's disease",

author = "Blanchet, {Pierre J.} and Fr{\'e}d{\'e}ric Calon and Marc Morissette and Tahar, {Abdallah Hadj} and Nancy B{\'e}langer and Pershia Samadi and Richard Grondin and Laurent Gr{\'e}goire and Leonard Meltzer and {Di Paolo}, Th{\'e}r{\`e}se and B{\'e}dard, {Paul J.}",

note = "Funding Information: This work was supported by grants from the Canadian Institutes for Health Research (CIHR) to P. Bedard and T. Di Paolo. F. Calon was the recipient of a health professional studentship from Novartis in partnership with CIHR and the Quebec Health Research Fund (FRSQ). The Authors are also grateful to Dr Ali H. Rajput, Royal University Hospital, University of Saskatchewan, for providing human brain tissue. Mrs M.-T. Parent kindly provided assistance in the preparation of the manuscript. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.; Striatal Plasticity in Health and Disease ; Conference date: 28-11-2003 Through 29-11-2003",

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language = "English",

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AU - Blanchet, Pierre J.

AU - Calon, Frédéric

AU - Morissette, Marc

AU - Tahar, Abdallah Hadj

AU - Bélanger, Nancy

AU - Samadi, Pershia

AU - Grondin, Richard

AU - Grégoire, Laurent

AU - Meltzer, Leonard

AU - Di Paolo, Thérèse

AU - Bédard, Paul J.

N1 - Funding Information: This work was supported by grants from the Canadian Institutes for Health Research (CIHR) to P. Bedard and T. Di Paolo. F. Calon was the recipient of a health professional studentship from Novartis in partnership with CIHR and the Quebec Health Research Fund (FRSQ). The Authors are also grateful to Dr Ali H. Rajput, Royal University Hospital, University of Saskatchewan, for providing human brain tissue. Mrs M.-T. Parent kindly provided assistance in the preparation of the manuscript. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2004/7

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N2 - For nearly 20 years, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model has allowed great strides to be made in our understanding of the maladaptive changes underlying the levodopa-related motor response complications occurring in most parkinsonian patients. Studies indicate that sustained dopamine D2 receptor occupancy can prevent and reverse existing dyskinesias. Recent experiments in levodopa-treated MPTP animals, co-administered either a threshold dose of cabergoline or a glutamate NMDA NR2B-selective antagonist (CI-1041), have afforded protection against dyskinesia, perhaps through presynaptic inhibition of glutamate release and blockade of supersensitive postsynaptic NMDA receptors in the striatum, respectively. Some of the biochemical events that have correlated with dyskinesias, namely upregulated GABAA receptors in the internal pallidum, rise in pre-proenkephalin-A gene expression in the striatum, and upregulated striatal glutamate ionotropic receptors and adenosine A2a receptors, may be counteracted by these preventive strategies.

AB - For nearly 20 years, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model has allowed great strides to be made in our understanding of the maladaptive changes underlying the levodopa-related motor response complications occurring in most parkinsonian patients. Studies indicate that sustained dopamine D2 receptor occupancy can prevent and reverse existing dyskinesias. Recent experiments in levodopa-treated MPTP animals, co-administered either a threshold dose of cabergoline or a glutamate NMDA NR2B-selective antagonist (CI-1041), have afforded protection against dyskinesia, perhaps through presynaptic inhibition of glutamate release and blockade of supersensitive postsynaptic NMDA receptors in the striatum, respectively. Some of the biochemical events that have correlated with dyskinesias, namely upregulated GABAA receptors in the internal pallidum, rise in pre-proenkephalin-A gene expression in the striatum, and upregulated striatal glutamate ionotropic receptors and adenosine A2a receptors, may be counteracted by these preventive strategies.

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KW - Dyskinesia

KW - Parkinson's disease

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Y2 - 28 November 2003 through 29 November 2003

ER -

Relevance of the MPTP primate model in the study of dyskinesia priming mechanisms

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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