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

Journal article

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.

Authors: Tan, S; Hartung, H; Visser-Vandewalle, V; Steinbusch, H; Temel, Y

• Publication status: Published
• Journal: Experimental neurology
• Volume: 233
• Issue: 1
• Pages: 145-153
• Publication date: 2012-01-01
• DOI: 10.1016/j.expneurol.2011.08.027
• EISSN: 1090-2430
• ISSN: 0014-4886
• Language: English
• Keywords: Animals; Adrenergic Agents; Dopamine; Parkinson Disease; Action Potentials; Electrochemistry; Disease Models, Animal; Male; Neurons; Brain; Microdialysis; Deep Brain Stimulation; Rats; Rats, Sprague-Dawley; Synaptic Transmission; Serotonin; Wakefulness; Analysis of Variance; Extracellular Fluid; Time Factors; Chromatography, High Pressure Liquid; Oxidopamine; Subthalamic Nucleus; Biophysics