Decreased striatal dopamine receptor binding in primary focal dystonia: A D2 or D3 defect?

Morvarid Karimi, Stephen M. Moerlein, Tom O. Videen, Robert R. Luedtke, Michelle Taylor, Robert H. Mach, Joel S. Perlmutter

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Dystonia is an involuntary movement disorder characterized by repetitive patterned or sustained muscle contractions causing twisting or abnormal postures. Several lines of evidence suggest that abnormalities of dopaminergic pathways contribute to the pathophysiology of dystonia. In particular, dysfunction of D2-like receptors that mediate function of the indirect pathway in the basal ganglia may play a key role. We have demonstrated with positron emission tomography that patients with primary focal cranial or hand dystonia have reduced putamenal specific binding of [18F]spiperone, a nonselective D2-like radioligand with nearly equal affinity for serotonergic 5-HT(2A) sites. We then repeated the study with [18F]N-methyl-benperidol (NMB), a more selective D2-like receptor radioligand with minimal affinity for 5-HT(2A). Surprisingly, there was no decrease in NMB binding in the putamen of subjects with dystonia. Our findings excluded reductions of putamenal uptake greater than 20% with 95% confidence intervals. The analysis of the in vitro selectivity of NMB and spiperone demonstrated that NMB was highly selective for D2 receptors relative to D3 receptors (200-fold difference in affinity), whereas spiperone has similar affinity for all three of the D2-like receptor subtypes. These findings when coupled with other literature suggest that a defect in D3, rather than D2, receptor expression may be associated with primary focal dystonia.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalMovement Disorders
Volume26
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • D2-like dopamine receptors
  • D3 dopamine receptor
  • Dopamine
  • Dystonia
  • NMB
  • PET

Fingerprint Dive into the research topics of 'Decreased striatal dopamine receptor binding in primary focal dystonia: A D2 or D3 defect?'. Together they form a unique fingerprint.

  • Cite this

    Karimi, M., Moerlein, S. M., Videen, T. O., Luedtke, R. R., Taylor, M., Mach, R. H., & Perlmutter, J. S. (2011). Decreased striatal dopamine receptor binding in primary focal dystonia: A D2 or D3 defect? Movement Disorders, 26(1), 100-106. https://doi.org/10.1002/mds.23401