title: A combined in vivo neurochemical and electrophysiological analysis of the effect of high-frequency stimulation of the subthalamic nucleus on 5-HT transmission.
abstract: 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.affiliation: Department of Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Sonny K H
authors.initials: SK
authors.lastname: Tan
authors.forename: Henrike
authors.initials: H
authors.lastname: Hartung
authors.forename: Veerle
authors.initials: V
authors.lastname: Visser-Vandewalle
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Yasin
authors.initials: Y
authors.lastname: Temel
authors.forename: Trevor
authors.initials: T
authors.lastname: Sharp
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D045604:Extracellular Fluid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D018663:Adrenergic Agents; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine