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Striatal dopamine D1-like receptor binding is unchanged in primary focal dystonia

Authors

  • Morvarid Karimi MD,

    Corresponding author
    1. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA
    • Correspondence to: Dr. Morvarid Karimi, 660 S. Euclid, Campus Box 8111, St. Louis, MO 63110-1093; morvaridk@npg.wustl.edu

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  • Stephen M. Moerlein PhD,

    1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Tom O. Videen PhD,

    1. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Yi Su PhD,

    1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Hubert P. Flores MS,

  • Joel S. Perlmutter MD

    1. Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA
    2. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    3. Department of Neurobiology, Washington University School of Medicine, Saint Louis, Missouri, USA
    4. Occupational Therapy Program, Washington University School of Medicine, Saint Louis, Missouri, USA
    5. Physical Therapy Program, Washington University School of Medicine, Saint Louis, Missouri, USA
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  • Funding agencies: This study was supported by the National Institutes of Health (grants K23NS069746, UL1 TR000448, NS41509, NS057105, and NS075321), the Murphy Fund, the American Parkinson Disease Association Center for Advanced Parkinson's Disease Research at Washington University, the Greater St. Louis Chapter of the American Parkinson Disease Association, the McDonnell Center for Higher Brain Function, and Barnes-Jewish Hospital Foundation.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background: Multiple studies have demonstrated decreases in striatal D2-like (D2, D3) radioligand binding in primary focal dystonias. Although most investigations have focused on D2-specific receptors (D2R), a recent study suggests that the decreased D2-like binding may be due to a D3-specific (D3R) abnormality. However, only limited data exist on the role of D1-specific receptors (D1R) and the D1R-mediated pathways within basal ganglia in dystonia. Metabolic positron emission tomography (PET) data in primary generalized dystonia suggest resting state over activity in the D1R-mediated direct pathway, leading to excessive disinhibition of motor cortical areas. This work investigated whether striatal D1-like receptors are affected in primary focal dystonias. Methods: Striatal-specific (caudate and putamen) binding of the D1-like radioligand [11C]NNC 112 was measured using PET in 19 patients with primary focal dystonia (cranial, cervical, or arm) and 18 controls. Results: No statistically significant difference was detected in striatal D1-like binding between the two groups. The study had 91% power to detect a 20% difference, indicating that false-negative results were unlikely. Conclusions: Because [11C]NNC 112 has high affinity for D1-like receptors, very low affinity for D2-like receptors, and minimal sensitivity to endogenous dopamine levels, we conclude that D1-like receptor binding is not impaired in these primary focal dystonias. © 2013 International Parkinson and Movement Disorder Society

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