Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: Potential mechanism of action in Parkinson's disease

Kendall H Lee, Charles D. Blaha, Brent T. Harris, Shannon Cooper, Frederick L. Hitti, James C. Leiter, David W. Roberts, Uhnoh Kim

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The precise mechanism whereby continuous high-frequency electrical stimulation of the subthalamic nucleus ameliorates motor symptoms of Parkinson's disease is unknown. We examined the effects of high-frequency stimulation of regions dorsal to and within the subthalamic nucleus on dopamine efflux in the striatum of urethane-anaesthetized rats using constant potential amperometry. Complementary extracellular electrophysiological studies determined the activity of subthalamic nucleus neurons in response to similar electrical stimulation of the subthalamic nucleus. High-frequency stimulation of the subthalamic nucleus increased action potential firing in the subthalamic nucleus only during the initial stimulation period and was followed by a cessation of firing over the remainder of stimulation. Electrical stimulation of the subthalamic nucleus with 15 pulses elicited stimulus-time-locked increases in striatal dopamine efflux with maximal peak effects occurring at 50 Hz frequency and 300 μA intensity. Extended subthalamic nucleus stimulation (1000 pulses at 50 Hz; 300 μA) elicited a similar peak increase in striatal dopamine efflux that was followed by a relatively lower steady-state elevation in extracellular dopamine over the course of stimulation. In contrast, extended stimulation immediately adjacent and dorsal to the subthalamic nucleus resulted in an 11-fold greater increase in dopamine efflux that remained elevated over the course of the stimulation. Immunohistochemical staining for tyrosine hydroxylase revealed catecholaminergic fibers running immediately dorsal to and through the subthalamic nucleus. Taken together, these results suggest that enhanced dopamine release within the basal ganglia may be an important mechanism whereby high-frequency stimulation of the subthalamic nucleus improves motor symptoms of Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)1005-1014
Number of pages10
JournalEuropean Journal of Neuroscience
Volume23
Issue number4
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Subthalamic Nucleus
Electric Stimulation
Action Potentials
Parkinson Disease
Dopamine
Corpus Striatum
Urethane
Tyrosine 3-Monooxygenase
Basal Ganglia

Keywords

  • Amperometry
  • Deep brain stimulation
  • Electrophysiology
  • High frequency stimulation
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus : Potential mechanism of action in Parkinson's disease. / Lee, Kendall H; Blaha, Charles D.; Harris, Brent T.; Cooper, Shannon; Hitti, Frederick L.; Leiter, James C.; Roberts, David W.; Kim, Uhnoh.

In: European Journal of Neuroscience, Vol. 23, No. 4, 02.2006, p. 1005-1014.

Research output: Contribution to journalArticle

Lee, Kendall H ; Blaha, Charles D. ; Harris, Brent T. ; Cooper, Shannon ; Hitti, Frederick L. ; Leiter, James C. ; Roberts, David W. ; Kim, Uhnoh. / Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus : Potential mechanism of action in Parkinson's disease. In: European Journal of Neuroscience. 2006 ; Vol. 23, No. 4. pp. 1005-1014.
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