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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.

Original publication

DOI

10.1016/j.expneurol.2011.08.027

Type

Journal article

Journal

Exp Neurol

Publication Date

01/2012

Volume

233

Pages

145 - 153

Keywords

Action Potentials, Adrenergic Agents, Analysis of Variance, Animals, Biophysics, Brain, Chromatography, High Pressure Liquid, Deep Brain Stimulation, Disease Models, Animal, Dopamine, Electrochemistry, Extracellular Fluid, Male, Microdialysis, Neurons, Oxidopamine, Parkinson Disease, Rats, Rats, Sprague-Dawley, Serotonin, Subthalamic Nucleus, Synaptic Transmission, Time Factors, Wakefulness