Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients.
File(s)
Published version
Author(s)
Politis, M
Wilson, H
Wu, K
Brooks, DJ
Piccini, P
Type
Journal Article
Abstract
We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [(11)C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [(11)C]raclopride non-displaceable binding potential were generated from the dynamic [(11)C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [(11)C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.
Date Issued
2017-08-24
Date Acceptance
2017-08-12
Citation
NeuroImage: Clinical, 2017, 16, pp.455-460
ISSN
2213-1582
Publisher
Elsevier
Start Page
455
End Page
460
Journal / Book Title
NeuroImage: Clinical
Volume
16
Copyright Statement
© 2017 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Identifier
PII: S2213-1582(17)30201-2
Subjects
AIMS, Abnormal Involuntary Movement Scale
BDI-II, Beck Depression Inventory
BPND, non-displaceable binding potential
Basal ganglia
D2R, dopamine receptor type-2
Dopamine D2 receptors
Dopamine agonists
H&Y, Hoehn and Yahr staging
LED, levodopa-equivalent-dose
MMSE, Mini-Mental State Examination
MRI, magnetic resonance imaging
PD, Parkinson's disease
PET
PET, position emission tomography
Parkinson's disease
ROI, region of interest
UPDRS, Unified Parkinson's Disease Rating Scale
Publication Status
Published online