Stimulation of the subthalamic nucleus in Parkinson's disease does not produce striatal dopamine release.
OBJECTIVE
The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson's disease (PD). The mechanism by which electrical stimulation of the STN ameliorates symptoms of PD remains unknown. One consistent aspect of STN stimulation is the ability to reduce the dosage of dopaminergic medications; sometimes they can be eliminated altogether. Furthermore, nigrostriatal projection axons are apposed to the dorsal surface of the STN and are likely affected by the application of current in this region. We sought to determine whether STN stimulation could release endogenous striatal dopamine.


METHODS
Five patients with PD, who had previously undergone surgical implantation of bilateral STN stimulators, underwent [(11)C]raclopride positron emission tomographic scanning. l-dopa was withheld for 12 hours, and both stimulators were turned off 9 hours before scanning. We assayed for striatal dopamine release by measuring radioligand displacement as a consequence of turning on the right STN stimulator after 45 minutes of a 90-minute [(11)C]raclopride infusion. Patients were evaluated with the motor section of the Unified Parkinson's Disease Rating Scale before and after the studies.


RESULTS
Comparisons between the right and left striata, before and after right STN stimulation, demonstrated no significant differences in [(11)C]raclopride binding, despite significant improvements in Unified Parkinson's Disease Rating Scale motor scores with unilateral stimulation (mean improvement, 26.0 +/- 16.4%; P < 0.05). This finding was also noted when the striatum was partitioned into dorsal and ventral caudate and putamen and the four regions were analyzed separately.


CONCLUSIONS
Our results suggest that STN stimulation does not mediate its anti-PD effects via the release of dopamine, as assessed with [(11)C]raclopride displacement.
Department of Surgery, Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, and University Health Network, University of Toronto, Toronto, Ontario, Canada. aabosch@emory.edu
Aviva
A
Abosch
Shitij
S
Kapur
Anthony E
AE
Lang
Doug
D
Hussey
Elspeth
E
Sime
Janis
J
Miyasaki
Sylvain
S
Houle
Andres M
AM
Lozano
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D004599:Electric Stimulation Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D020891:Raclopride; D020531:Subthalamic Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D018492:Dopamine Antagonists; D020891:Raclopride; D004298:Dopamine