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Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission.

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Title: Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission.
Authors: Gubellini, Paolo (AUTHOR), Eusebio, Alexandre (AUTHOR), Oueslati, Abid (AUTHOR), Melon, Christophe (AUTHOR), Kerkerian‐Le Goff, Lydia (AUTHOR), Salin, Pascal (AUTHOR)
Source: European Journal of Neuroscience. Sep2006, Vol. 24 Issue 6, p1802-1814. 13p. 1 Diagram, 1 Chart, 7 Graphs.
Subjects: Cell nuclei, Neurons, Dopa, Parkinson's disease, Synapses
Abstract: Hyperactivity of striatal glutamatergic synaptic transmission in response to dopamine depletion plays a major role in the pathogenesis of parkinsonian motor symptoms. In the present study we investigated the impact, on this hyperactivity, of chronic dyskinesiogenic L-DOPA treatment, combined or not with high-frequency stimulation (HFS) of the subthalamic nucleus (STN). In vitro patch-clamp recordings were performed from striatal spiny neurons of hemiparkinsonian rats (intranigral 6-OHDA injection). Here we show that dyskinesiogenic L-DOPA treatment exacerbated striatal glutamatergic hyperactivity induced by 6-OHDA lesion. Chronic 5-day STN HFS had the opposite effect, reducing striatal glutamatergic transmission in both parkinsonian and dyskinetic animals. Consistently, chronic HFS stimulation could progressively ameliorate motor parkinsonian signs (akinesia) but, conversely, did not improve L-DOPA-induced dyskinesia (LID). Thus, the effects of L-DOPA and HFS on corticostriatal transmission seem to be dissociated. These data show for the first time that dyskinesiogenic L-DOPA treatment and chronic STN HFS with antiakinetic effects induce opposite plastic rearrangements in the striatum. The interaction between these two treatments provides further evidence that striatal glutamatergic hyperactivity is a pathophysiological correlate of akinesia rather than LID. [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: Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission.
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  Data: <searchLink fieldCode="AR" term="%22Gubellini%2C+Paolo%22">Gubellini, Paolo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Eusebio%2C+Alexandre%22">Eusebio, Alexandre</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Oueslati%2C+Abid%22">Oueslati, Abid</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Melon%2C+Christophe%22">Melon, Christophe</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kerkerian‐Le+Goff%2C+Lydia%22">Kerkerian‐Le Goff, Lydia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Salin%2C+Pascal%22">Salin, Pascal</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Sep2006, Vol. 24 Issue 6, p1802-1814. 13p. 1 Diagram, 1 Chart, 7 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Cell+nuclei%22">Cell nuclei</searchLink><br /><searchLink fieldCode="DE" term="%22Neurons%22">Neurons</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="%22Synapses%22">Synapses</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Hyperactivity of striatal glutamatergic synaptic transmission in response to dopamine depletion plays a major role in the pathogenesis of parkinsonian motor symptoms. In the present study we investigated the impact, on this hyperactivity, of chronic dyskinesiogenic L-DOPA treatment, combined or not with high-frequency stimulation (HFS) of the subthalamic nucleus (STN). In vitro patch-clamp recordings were performed from striatal spiny neurons of hemiparkinsonian rats (intranigral 6-OHDA injection). Here we show that dyskinesiogenic L-DOPA treatment exacerbated striatal glutamatergic hyperactivity induced by 6-OHDA lesion. Chronic 5-day STN HFS had the opposite effect, reducing striatal glutamatergic transmission in both parkinsonian and dyskinetic animals. Consistently, chronic HFS stimulation could progressively ameliorate motor parkinsonian signs (akinesia) but, conversely, did not improve L-DOPA-induced dyskinesia (LID). Thus, the effects of L-DOPA and HFS on corticostriatal transmission seem to be dissociated. These data show for the first time that dyskinesiogenic L-DOPA treatment and chronic STN HFS with antiakinetic effects induce opposite plastic rearrangements in the striatum. The interaction between these two treatments provides further evidence that striatal glutamatergic hyperactivity is a pathophysiological correlate of akinesia rather than LID. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  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.1460-9568.2006.05047.x
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              Text: Sep2006
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