Upregulation of dopamine D2 receptors in dopaminergic drug-naive patients with parkin gene mutations

Authors

  • Christoph Scherfler MD,

    Corresponding author
    1. MRC Clinical Science Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    • Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
    Search for more papers by this author
  • Naheed L. Khan MB,

    1. Department of Molecular Pathogenesis, Institute of Neurology, London, United Kingdom
    Search for more papers by this author
  • Nicola Pavese MD,

    1. MRC Clinical Science Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    Search for more papers by this author
  • Andrew J. Lees MD,

    1. Reta Lila Weston Institute of Neurological Studies, Royal Free Hospital and University College Medical School, London, United Kingdom
    Search for more papers by this author
  • Niall P. Quinn MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, United Kingdom
    Search for more papers by this author
  • David J. Brooks DSc,

    1. MRC Clinical Science Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    Search for more papers by this author
  • Paola P. Piccini MD, PhD

    1. MRC Clinical Science Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    Search for more papers by this author

Abstract

Medicated patients with Parkinsonism and parkin gene mutations have been reported to show a significant decrease in striatal dopamine D2 receptors (D2R) in comparison to medicated idiopathic Parkinson's disease (IPD) patients with similar age and disease severity. The aim of this study was to verify whether the genetic defect per se is responsible for this decrease. We have studied with [11C]raclopride (RAC) positron emission tomography (PET) in a group of 14 sporadic patients with parkin-linked Parkinsonism, 6 of whom had never received levodopa or dopamine agonists. The remaining 8 patients had been treated with levodopa for at least 5 years. Presynaptic striatal [18F]dopa storage was not significantly different between these two groups of patients. In untreated parkin-positive patients, significant putaminal increases in RAC-binding potential (BP) were found in comparison to an age-matched healthy control group by using a classical region of interest approach and statistical parametric mapping. In contrast, levodopa-treated parkin-positive patients showed significant decreases in RAC-BP in the caudate and putamen when compared to an age-matched healthy control group. The RAC PET findings revealed that striatal D2R upregulation occurs in dopaminergic drug-naive parkin-positive patients, in a similar fashion to the upregulation reported in drug-naive IPD. D2R downregulation observed in medicated parkin-positive patients, therefore, is not caused primarily by the genetic defect itself. Parkin-positive patients appear to have a greater susceptibility to the exposure to dopaminergic medication than IPD patients, which in turn might be an indirect effect of their genetic mutation. © 2006 Movement Disorder Society

Ancillary