Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans.
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.
Hilker
Ruediger
R
Department of Neurology, University Hospital, Cologne, Germany. hilker@pet.mpin-koeln.mpg.de
Voges
Juergen
J
Ghaemi
Mehran
M
Lehrke
Ralf
R
Rudolf
Jobst
J
Koulousakis
Athanasios
A
Herholz
Karl
K
Wienhard
Klaus
K
Sturm
Volker
V
Heiss
Wolf-Dieter
WD
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
D020891:Raclopride; D004298:Dopamine