Downregulation of Striatal Dopamine D2 Receptors in Advanced Parkinson’s Disease Contributes to the Development of Motor FluctuationHwang W.-J.a · Yao W.-J.b · Wey S.-P.c · Shen L.-H.c · Ting G.c
Departments of aNeurology, bNuclear Medicine, College of Medicine, National Cheng Kung University, Tainan, and cInstitute of Nuclear Energy Research, Lung-Tan, Taiwan
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
The purpose of this study was to evaluate the contribution of the postsynaptic mechanism to the development of motor fluctuation in advanced Parkinson’s disease (PD). We used 123I-iodobenzamide single-photon emission computed tomography to measure the striatal dopamine D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres were calculated and averaged. PD patients with fluctuating levodopa response showed a significant decrease in striatal dopamine D2 receptor densities compared to those with early (1.57 ± 0.20 vs. 1.77 ± 0.12, p = 0.009) or chronic stable PD (1.57 ± 0.20 vs. 1.77 ± 0.10, p = 0.024). We conclude that the decreased D2 receptor densities in advanced PD reduced the ‘safety factor’ for synaptic transmission and contributed to the development of motor fluctuation.
© 2002 S. Karger AG, Basel
- Wang SJ, Fuh JL, Teng EL, Liu CY, Lin KP, Chen HM, Lin CH, Wang PN, Ting YC, Wang HC: A door-to-door survey of Parkinson’s disease in a Chinese population in Kinmen. Arch Neurol 1996;53:66–71.
- Contin M, Riva R, Martinelli P, Cortelli P, Albani F, Baruzzi A: Longitudinal monitoring of the levodopa concentration-effect relationship in Parkinson’s disease. Neurology 1994;44:1287–1292.
- Leenders KL, Palmer AJ, Quinn N, Clark JC, Firnau G, Garnett ES, Nahmias C, Jones T, Marsden CD: Brain dopamine metabolism in patients with Parkinson’s disease measured with positron emission tomography. J Neurol Neurosurg Psychiatry 1986;49:853–860.
- Cedarbaum JM, Olanow CW: Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson’s disease. Neurology 1991;41:1567–1570.
- Fabbrini G, Mouradian MM, Juncos JL, Schlegel J, Mohr E, Chase TN: Motor fluctuations in Parkinson’s disease: Central pathophysiological mechanisms, Part I. Ann Neurol 1988;24:366–371.
- Bravi D, Mouradian MM, Roberts JW, Davis TL, Sohn YH, Chase TN: Wearing-off fluctuations in Parkinson’s disease: Contribution of postsynaptic mechanisms. Ann Neurol 1994;36:27–31.
- Antonini A, Schwarz J, Oertel WH, Pogarell O, Leenders KL: Long-term changes of striatal dopamine D2 receptors in patients with Parkinson’s disease: a study with positron emission tomography and [11C]raclopride. Mov Disord 1997;12:33–38.
- Schwarz J, Antonini A, Tatsch K, Kirsch CM, Oertel WH, Leenders KL: Comparison of 123I-IBZM SPECT and 11C-raclopride PET findings in patients with parkinsonism. Nucl Med Commun 1994;15:806–813.
- Laulumaa V, Kuikka JT, Soininen H, Bergstrom K, Lansimies E, Riekkinen P: Imaging of D2 dopamine receptors of patients with Parkinson’s disease using single photon emission computed tomography and iodobenzamide 123I. Arch Neurol 1993;50:509–512.
- Pizzolato G, Chierichetti F, Rossato A, Cagnin A, Fabbri M, Dam M, Ferlin G, Battistin L: Alterations of striatal dopamine D2 receptors contribute to deteriorated response to L-dopa in Parkinson’s disease: A [123I]-IBZM SPET study. J Neural Transm Suppl 1995;45:113–122.
- Pizzolato G, Chierichetti F, Rossato A, Briani C, Dam M, Borsato N, Saitta B, Zanco P, Ferlin G, Battistin L: Dopamine receptor SPET imaging in Parkinson’s disease: A [123I]-IBZM and [99mTc]-HM-PAO study. Eur Neurol 1993;33:143–148.
- Brooks DJ, Ibanez V, Sawle GV, Playford ED, Quinn N, Mathias CJ, Lees AJ, Marsden CD, Bannister R, Frackowiak RSJ: Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol 1992;31:184–192.
- Langston JW, Widner H, Goetz CG, Brooks DJ, Fahn S, Freeman T, Watts R: Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 1992;7:2–13.
Schwarz J, Oertel WH, Tatsch K: Iodine-123-iodobenzamide binding in parkinsonism: Reduction by dopamine agonists but not L-dopa. J Nucl Med 1996;37:112–115.
- Kung MP, Liu BL, Yang YY, Billings JJ, Kung HF: A kit formulation for preparation of 123I-IBZM: A new CNS D2 dopamine receptor imaging agent. J Nucl Med 1991;32:339–342.
- Leslie WD, Abrams DN, Greenberg CR, Hobson D: Comparison of 123I-epidepride and 123I-IBZM for dopamine D2 receptor imaging. J Nucl Med 1996;37:1589–1591.
Chang LT: A method for attenuation correction in radionuclide computed tomography. IEEE NS 1978;25:638–639.
- Nutt JG, Carter JH, Lea ES, Woodward WR: Motor fluctuations during continuous levodopa infusions in patients with Parkinson’s disease. Mov Disord 1997;12:285–292.
- Mouradian MM, Heuser IJE, Baronti F, Chase TN: Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson’s disease. Ann Neurol 1990;27:18–23.
- Rinne UK, Lönnberg P, Koskinen V: Dopamine receptors in the parkinsonian brain. J Neural Transm 1981;51:97–106.
Oh SJ: Electromyography: Neuromuscular Transmission Studies. Baltimore, Williams & Wilkins, 1988, pp 1–29.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.