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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Christoph Scherfler, Imperial College London, London, UK., Medical University of Innsbruck
  • ,
  • Naheed L. Khan, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London
  • ,
  • Nicola Pavese
  • Andrew J. Lees, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London
  • ,
  • Niall P. Quinn, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London
  • ,
  • David J. Brooks
  • Paola P. Piccini, Imperial College London, London, UK.

Medicated patients with Parkinsonism and parkin gene mutationls 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.

Original languageEnglish
JournalMovement Disorders
Volume21
Issue6
Pages (from-to)783-788
Number of pages6
ISSN0885-3185
DOIs
Publication statusPublished - 1 Jun 2006
Externally publishedYes

    Research areas

  • [C]raclopride, [F]dopa, Dopamine D receptors, Parkin gene mutation, Parkinson's disease, Positron emission tomography

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