High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats
Article first published online: 14 APR 2003
Journal of Neurochemistry
Volume 85, Issue 3, pages 601–609, May 2003
How to Cite
Meissner, W., Harnack, D., Reese, R., Paul, G., Reum, T., Ansorge, M., Kusserow, H., Winter, C., Morgenstern, R. and Kupsch, A. (2003), High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats. Journal of Neurochemistry, 85: 601–609. doi: 10.1046/j.1471-4159.2003.01665.x
- Issue published online: 14 APR 2003
- Article first published online: 14 APR 2003
- Received May 21, 2002; revised manuscript received November 20, 2002; accepted December 19, 2002.
- deep-brain stimulation;
- Parkinson's disease;
- tyrosine hydroxylase
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.