A combined in vivo neurochemical and electrophysiological analysis of the effect of high-frequency stimulation of the subthalamic nucleus on 5-HT transmission

Sonny K. H. Tan, Henrike Hartung, Veerle Visser-Vandewalle, Harry W. M. Steinbusch, Yasin Temel, Trevor Sharp*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Movement disability in advanced Parkinson's disease (PD) can be treated by high frequency stimulation (HFS) of the subthalamic nucleus (STN) but some patients experience psychiatric side-effects including depression, which is strongly linked to decreases in 5-hydroxytryptamine (5-HT). The current study investigated the effect of bilateral STN HFS on extracellular 5-HT in brain regions of anesthetized and freely moving rats as measured with microdialysis. Parallel in vivo electrophysiological experiments allowed a correlation of changes in extracellular 5-HT with the firing of 5-HT neurons. Bilateral STN HFS decreased (by up to 25%) extracellular levels of 5-HT in both striatum and medial prefrontal cortex of anesthetized rats. STN HFS also decreased extracellular 5-HT in the medial prefrontal cortex of freely moving rats. This decrease in extracellular 5-HT persisted after turning off the stimulation, and was present in dopamine-denervated rats. As with changes in extracellular 5-HT, in anesthetized rats STN HFS evoked a decrease in the in vivo firing of midbrain raphe 5-HT neurons that also persisted after cessation of stimulation. These data provide neurochemical evidence for an inhibition of 5-HT neurotransmission by STN HFS, which may contribute to its psychiatric side effects and guide therapeutic options. Crown
Original languageEnglish
Pages (from-to)145-153
JournalExperimental Neurology
Issue number1
Publication statusPublished - Jan 2012


  • Parkinson's disease
  • Deep brain stimulation
  • Subthalamic nucleus
  • Depression
  • 5-HT
  • Microdialysis
  • In vivo electrophysiology

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