Article

Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson's disease - A [C-11]-raclopride PET study

CERMEP, Брон, Rhône-Alpes, France
Journal of Neurology (Impact Factor: 3.84). 11/2003; 250(10):1219-23. DOI: 10.1007/s00415-003-0188-z
Source: PubMed

ABSTRACT Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported.
To determine in Parkinson's disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release.
Nine PD patients with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping.
For PD patients, the mean [(11C]-Raclopride BP (+/- SD) were, in Off stimulation condition: 1.7 +/- 0.3 for the right caudate nucleus, 1.8 +/- 0.4 for the left caudate nucleus, 2.6 +/- 0.5 for the right putamenand 2.6 +/- 0.5 for the left putamen. In On stimulation condition: 1.7 +/- 0.4 for the right caudate nucleus, 1.9 +/- 0.5 for the left caudate nucleus, 2.8 +/- 0.7 for the right putamen and 2.7 +/- 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted.
STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.

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    • "Binding of this tracer is inversely proportional to levels of extracellular dopamine (Laruelle, 2000). After a period when the stimulation has been turned off and L-dopa withdrawn, STN-HFS in one side does not induce differences in [ 11 C] raclopride binding between the two striata (Abosch et al., 2003; Hilker et al., 2003b; Strafella et al., 2003b; Thobois et al., 2003). Therefore, there is no evidence for STN stimulation inducing dopamine release in humans. "
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    • "Another study also indicated that STN HFS in MPTP-treated monkeys provided about 20% neuroprotection to DAergic cells (Wallace et al., 2007). Thus, although clinical findings reported that STN HFS failed to improve DA outflow in PD patients or increase the survival of DAergic cells (Hilker et al., 2003; Thobois et al., 2003), most of the studies in animal models with partial DA lesion are in agreement with an activation/preservation of the DAergic system by STN HFS. However, this effect is unlikely to participate to the thera­ peutic action in late stages of PD, when patients usually undergo HFS, due to the already extensive loss of DAergic neurons. "
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    • "Some animal studies have suggested that STN DBS could increase the extracellular content of striatal dopamine release (Bruet et al, 2001). However this was not confirmed using PET studies and [ 11 C]-raclopride, a D2 dopamine antagonist ligand (Strafella et al, 2003b; Thobois et al, 2003). Nevertheless, this does not rule out the idea of increased striatal DA release with STN DBS. "
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