title: Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans.
abstract: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an effective treatment option in advanced Parkinson's disease (PD). Recent animal studies showed an increase of neuronal firing in dopaminergic neurons under effective STN-DBS. Increased striatal dopamine levels may also contribute to the stimulation's mechanism of action in humans. We investigated the striatal dopamine release in 6 patients with advanced PD under effective bilateral STN-DBS with positron emission tomography (PET) of the reversible dopamine-D2/3-receptor ligand [(11)C]raclopride (RACLO). Although STN-DBS proved to be a highly effective treatment in these subjects, we found no significant difference of the striatal RACLO binding between the STN-DBS-on and -off condition. The changes of radioligand binding did not correlate with the patients' improvement in clinical rating scales or with the stimulation amplitudes. Therefore, our PET data in living parkinsonian humans do not provide evidence for an increased striatal dopamine concentration under effective STN-DBS. We conclude that the modulation of dopaminergic activity does not seem to play a crucial role for the stimulation's mechanisms of action in parkinsonian humans.
authors.affiliation: Department of Neurology, University Hospital, Cologne, Germany. hilker@pet.mpin-koeln.mpg.de
authors.forename: Ruediger
authors.initials: R
authors.lastname: Hilker
authors.forename: Juergen
authors.initials: J
authors.lastname: Voges
authors.forename: Mehran
authors.initials: M
authors.lastname: Ghaemi
authors.forename: Ralf
authors.initials: R
authors.lastname: Lehrke
authors.forename: Jobst
authors.initials: J
authors.lastname: Rudolf
authors.forename: Athanasios
authors.initials: A
authors.lastname: Koulousakis
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Klaus
authors.initials: K
authors.lastname: Wienhard
authors.forename: Volker
authors.initials: V
authors.lastname: Sturm
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Heiss
mesh_terms: D000368:Aged; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D020891:Raclopride; D020531:Subthalamic Nucleus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
chemical_list: D020891:Raclopride; D004298:Dopamine