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Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-d-aspartate receptors.

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Title: Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-d-aspartate receptors.
Authors: Quintana, Adrien (AUTHOR), Melon, Christophe (AUTHOR), Goff, Lydia Kerkerian‐Le (AUTHOR), Salin, Pascal (AUTHOR), Savasta, Marc (AUTHOR), Sgambato‐Faure, Véronique (AUTHOR)
Source: European Journal of Neuroscience. Aug2010, Vol. 32 Issue 3, p423-434. 12p. 6 Graphs.
Subjects: Movement disorders, Dopa, Parkinson's disease, Methyl aspartate, Catecholamines, Subthalamic nucleus
Abstract: Dyskinesia is a major side-effect of chronicl-DOPA administration, the reference treatment for Parkinson’s disease. High-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates parkinsonian motor symptoms and indirectly improves dyskinesia by decreasing thel-DOPA requirement. However, inappropriate stimulation can also trigger dyskinetic movements, in both human and rodents. We investigated whether STN-HFS-evoked forelimb dyskinesia involved changes in glutamatergic neurotransmission as previously reported forl-DOPA-induced dyskinesias, focusing on the role of NR2B-containing N-methyl-d-aspartate receptors (NR2B/NMDARs). We applied STN-HFS in normal rats at intensities above and below the threshold for triggering forelimb dyskinesia. Dyskinesiogenic STN-HFS induced the activation of NR2B (as assessed by immunodetection of the phosphorylated residue Tyr1472) in neurons of the subthalamic nucleus, entopeduncular nucleus, motor thalamus and forelimb motor cortex. The severity of STN-HFS-induced forelimb dyskinesia was decreased in a dose-dependent manner by systemic injections of CP-101,606, a selective blocker of NR2B/NMDARs, but was either unaffected or increased by the non-selective N-methyl-d-aspartate receptor antagonist, MK-801. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
  Group: Ti
  Data: Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-d-aspartate receptors.
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  Data: <searchLink fieldCode="AR" term="%22Quintana%2C+Adrien%22">Quintana, Adrien</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Melon%2C+Christophe%22">Melon, Christophe</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Goff%2C+Lydia+Kerkerian‐Le%22">Goff, Lydia Kerkerian‐Le</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Salin%2C+Pascal%22">Salin, Pascal</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Savasta%2C+Marc%22">Savasta, Marc</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sgambato‐Faure%2C+Véronique%22">Sgambato‐Faure, Véronique</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Aug2010, Vol. 32 Issue 3, p423-434. 12p. 6 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Movement+disorders%22">Movement disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Dopa%22">Dopa</searchLink><br /><searchLink fieldCode="DE" term="%22Parkinson's+disease%22">Parkinson's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Methyl+aspartate%22">Methyl aspartate</searchLink><br /><searchLink fieldCode="DE" term="%22Catecholamines%22">Catecholamines</searchLink><br /><searchLink fieldCode="DE" term="%22Subthalamic+nucleus%22">Subthalamic nucleus</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Dyskinesia is a major side-effect of chronicl-DOPA administration, the reference treatment for Parkinson’s disease. High-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates parkinsonian motor symptoms and indirectly improves dyskinesia by decreasing thel-DOPA requirement. However, inappropriate stimulation can also trigger dyskinetic movements, in both human and rodents. We investigated whether STN-HFS-evoked forelimb dyskinesia involved changes in glutamatergic neurotransmission as previously reported forl-DOPA-induced dyskinesias, focusing on the role of NR2B-containing N-methyl-d-aspartate receptors (NR2B/NMDARs). We applied STN-HFS in normal rats at intensities above and below the threshold for triggering forelimb dyskinesia. Dyskinesiogenic STN-HFS induced the activation of NR2B (as assessed by immunodetection of the phosphorylated residue Tyr1472) in neurons of the subthalamic nucleus, entopeduncular nucleus, motor thalamus and forelimb motor cortex. The severity of STN-HFS-induced forelimb dyskinesia was decreased in a dose-dependent manner by systemic injections of CP-101,606, a selective blocker of NR2B/NMDARs, but was either unaffected or increased by the non-selective N-methyl-d-aspartate receptor antagonist, MK-801. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/j.1460-9568.2010.07290.x
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        Text: English
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      – SubjectFull: Movement disorders
        Type: general
      – SubjectFull: Dopa
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      – SubjectFull: Parkinson's disease
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      – SubjectFull: Catecholamines
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      – SubjectFull: Subthalamic nucleus
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    Titles:
      – TitleFull: Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-d-aspartate receptors.
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              Text: Aug2010
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