High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats.
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.
Meissner
Wassilios
W
Department of Neurology, Charité Campus Virchow, Humboldt-University Berlin, Germany. wassolios.meissner@charite.de
Harnack
Daniel
D
Reese
René
R
Paul
Gesine
G
Reum
Torsten
T
Ansorge
Mark
M
Kusserow
Heike
H
Winter
Christine
C
Morgenstern
Rudolf
R
Kupsch
Andreas
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009479:Neuropeptides; D009627:Nomifensine / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins
D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors; D009479:Neuropeptides; D012333:RNA, Messenger; D050492:Vesicular Biogenic Amine Transport Proteins; D009627:Nomifensine; D012110:Reserpine; D010293:Pargyline; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine