Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Brain/*metabolism ; Receptors, Dopamine D2/*metabolism ; Receptors, Dopamine D3/*metabolism; Animals ; Brain/blood supply ; Brain/drug effects ; Cerebrovascular Circulation/drug effects ; Dopamine Antagonists/administration & dosage ; Dopamine Antagonists/pharmacokinetics ; Dopamine D2 Receptor Antagonists ; Macaca mulatta ; Magnetic Resonance Imaging/methods ; Male ; Models, Neurological ; Positron-Emission Tomography/methods ; Raclopride/administration & dosage ; Raclopride/pharmacokinetics ; Receptors, Dopamine D3/antagonists & inhibitors
    • Abstract:
      This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [(11)C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.
    • Comments:
      Comment in: Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):10888-9. (PMID: 23784782)
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    • Grant Information:
      S10RR022976 United States RR NCRR NIH HHS; S10 RR022976 United States RR NCRR NIH HHS; P30DA28800 United States DA NIDA NIH HHS; S10RR026666 United States RR NCRR NIH HHS; R01 MH100350 United States MH NIMH NIH HHS; P30 DA028800 United States DA NIDA NIH HHS; P41 RR014075 United States RR NCRR NIH HHS; S10 RR026666 United States RR NCRR NIH HHS; R90DA023427 United States DA NIDA NIH HHS; P41RR14075 United States RR NCRR NIH HHS; S10RR019933 United States RR NCRR NIH HHS; S10 RR017208 United States RR NCRR NIH HHS; R90 DA023427 United States DA NIDA NIH HHS; S10RR017208 United States RR NCRR NIH HHS; S10 RR019933 United States RR NCRR NIH HHS; P41 EB015896 United States EB NIBIB NIH HHS
    • Contributed Indexing:
      Keywords: NHP; displacement; dynamic binding potential; monkey
    • Accession Number:
      0 (Dopamine Antagonists)
      0 (Dopamine D2 Receptor Antagonists)
      0 (Receptors, Dopamine D2)
      0 (Receptors, Dopamine D3)
      430K3SOZ7G (Raclopride)
    • Publication Date:
      Date Created: 20130601 Date Completed: 20130926 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      PMC3703969
    • Accession Number:
      10.1073/pnas.1220512110
    • Accession Number:
      23723346