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Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients.
Neuroimage Clin. 2017; 16:455-460.NC

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 [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]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 [11C]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.

Authors+Show Affiliations

Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK. Positron Emission Tomography Center, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28879087

Citation

Politis, Marios, et al. "Chronic Exposure to Dopamine Agonists Affects the Integrity of Striatal D2 Receptors in Parkinson's Patients." NeuroImage. Clinical, vol. 16, 2017, pp. 455-460.
Politis M, Wilson H, Wu K, et al. Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients. Neuroimage Clin. 2017;16:455-460.
Politis, M., Wilson, H., Wu, K., Brooks, D. J., & Piccini, P. (2017). Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients. NeuroImage. Clinical, 16, 455-460. https://doi.org/10.1016/j.nicl.2017.08.013
Politis M, et al. Chronic Exposure to Dopamine Agonists Affects the Integrity of Striatal D2 Receptors in Parkinson's Patients. Neuroimage Clin. 2017;16:455-460. PubMed PMID: 28879087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients. AU - Politis,Marios, AU - Wilson,Heather, AU - Wu,Kit, AU - Brooks,David J, AU - Piccini,Paola, Y1 - 2017/08/24/ PY - 2017/02/17/received PY - 2017/07/06/revised PY - 2017/08/12/accepted PY - 2017/9/8/entrez PY - 2017/9/8/pubmed PY - 2018/5/11/medline KW - AIMS, Abnormal Involuntary Movement Scale KW - BDI-II, Beck Depression Inventory KW - BPND, non-displaceable binding potential KW - Basal ganglia KW - D2R, dopamine receptor type-2 KW - Dopamine D2 receptors KW - Dopamine agonists KW - H&Y, Hoehn and Yahr staging KW - LED, levodopa-equivalent-dose KW - MMSE, Mini-Mental State Examination KW - MRI, magnetic resonance imaging KW - PD, Parkinson's disease KW - PET KW - PET, position emission tomography KW - Parkinson's disease KW - ROI, region of interest KW - UPDRS, Unified Parkinson's Disease Rating Scale SP - 455 EP - 460 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 16 N2 - 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 [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]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 [11C]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. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/28879087/Chronic_exposure_to_dopamine_agonists_affects_the_integrity_of_striatal_D2_receptors_in_Parkinson's_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(17)30201-2 DB - PRIME DP - Unbound Medicine ER -