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High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats

Meissner, Wassilios G.; Harnack, Daniel; Reese, René; Paul, Gesine LU ; Reum, Torsten; Ansorge, Mark; Kusserow, Heike; Winter, Christine; Morgenstern, Rudolf and Kupsch, Andreas (2003) In Journal of Neurochemistry 85(3). p.9-601
Abstract

High-frequency stimulation of the subthalamic nucleus is believed to exert its main effects via the basal ganglia output structures. Previously, we have shown a concomitant increase in striatal dopamine (DA) metabolites in normal and 6-hydroxydopamine-lesioned rats. The present study was designed to determine whether this increase in striatal DA metabolites reflects enhanced intraneuronal DA turnover or, alternatively, is due to increased DA release with subsequent rapid and efficient reuptake and/or metabolism. Thus, high-frequency stimulation of the subthalamic nucleus was performed in normal rats after inhibition of DA reuptake, metabolism or DA depletion. Extracellular levels of striatal DA and its metabolites were assessed using... (More)

High-frequency stimulation of the subthalamic nucleus is believed to exert its main effects via the basal ganglia output structures. Previously, we have shown a concomitant increase in striatal dopamine (DA) metabolites in normal and 6-hydroxydopamine-lesioned rats. The present study was designed to determine whether this increase in striatal DA metabolites reflects enhanced intraneuronal DA turnover or, alternatively, is due to increased DA release with subsequent rapid and efficient reuptake and/or metabolism. Thus, high-frequency stimulation of the subthalamic nucleus was performed in normal rats after inhibition of DA reuptake, metabolism or DA depletion. Extracellular levels of striatal DA and its metabolites were assessed using microdialysis. Our data suggest that subthalamic high-frequency stimulation increases striatal DA release and activates independent striatal DA metabolism. Since such changes could be triggered by modification of either the activity or the gene expression of the rate-limiting enzyme tyrosine hydroxylase, an activity assay and RT-PCR of striatal and nigral samples were performed. Subthalamic stimulation increased striatal tyrosine hydroxylase activity without affecting gene expression. We, therefore, conclude that the application of subthalamic high-frequency stimulation could partially compensate for the DA deficit by inducing increased striatal DA release and metabolism.

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published
keywords
Animals, Corpus Striatum, Dopamine, Dopamine Uptake Inhibitors, Electric Stimulation, Extracellular Space, Male, Membrane Glycoproteins, Membrane Transport Proteins, Microdialysis, Monoamine Oxidase Inhibitors, Neuropeptides, Nomifensine, Pargyline, RNA, Messenger, Rats, Rats, Wistar, Reference Values, Reserpine, Substantia Nigra, Subthalamic Nucleus, Tyrosine 3-Monooxygenase, Vesicular Biogenic Amine Transport Proteins, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neurochemistry
volume
85
issue
3
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0038674399
ISSN
0022-3042
language
English
LU publication?
no
id
6ee35afd-8e02-48ac-89c8-4339455d68af
date added to LUP
2017-05-18 11:27:27
date last changed
2017-07-09 05:01:07
@article{6ee35afd-8e02-48ac-89c8-4339455d68af,
  abstract     = {<p>High-frequency stimulation of the subthalamic nucleus is believed to exert its main effects via the basal ganglia output structures. Previously, we have shown a concomitant increase in striatal dopamine (DA) metabolites in normal and 6-hydroxydopamine-lesioned rats. The present study was designed to determine whether this increase in striatal DA metabolites reflects enhanced intraneuronal DA turnover or, alternatively, is due to increased DA release with subsequent rapid and efficient reuptake and/or metabolism. Thus, high-frequency stimulation of the subthalamic nucleus was performed in normal rats after inhibition of DA reuptake, metabolism or DA depletion. Extracellular levels of striatal DA and its metabolites were assessed using microdialysis. Our data suggest that subthalamic high-frequency stimulation increases striatal DA release and activates independent striatal DA metabolism. Since such changes could be triggered by modification of either the activity or the gene expression of the rate-limiting enzyme tyrosine hydroxylase, an activity assay and RT-PCR of striatal and nigral samples were performed. Subthalamic stimulation increased striatal tyrosine hydroxylase activity without affecting gene expression. We, therefore, conclude that the application of subthalamic high-frequency stimulation could partially compensate for the DA deficit by inducing increased striatal DA release and metabolism.</p>},
  author       = {Meissner, Wassilios G. and Harnack, Daniel and Reese, René and Paul, Gesine and Reum, Torsten and Ansorge, Mark and Kusserow, Heike and Winter, Christine and Morgenstern, Rudolf and Kupsch, Andreas},
  issn         = {0022-3042},
  keyword      = {Animals,Corpus Striatum,Dopamine,Dopamine Uptake Inhibitors,Electric Stimulation,Extracellular Space,Male,Membrane Glycoproteins,Membrane Transport Proteins,Microdialysis,Monoamine Oxidase Inhibitors,Neuropeptides,Nomifensine,Pargyline,RNA, Messenger,Rats,Rats, Wistar,Reference Values,Reserpine,Substantia Nigra,Subthalamic Nucleus,Tyrosine 3-Monooxygenase,Vesicular Biogenic Amine Transport Proteins,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {3},
  pages        = {9--601},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats},
  volume       = {85},
  year         = {2003},
}