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High-potency ligands for DREADD imaging and activation in rodents and monkeys

Author

Listed:
  • Jordi Bonaventura

    (National Institute on Drug Abuse Intramural Research Program)

  • Mark A. G. Eldridge

    (National Institute of Mental Health Intramural Research Program)

  • Feng Hu

    (Department of Radiology Johns Hopkins School of Medicine)

  • Juan L. Gomez

    (National Institute on Drug Abuse Intramural Research Program)

  • Marta Sanchez-Soto

    (National Institute of Neurological Disorders and Stroke Intramural Research Program)

  • Ara M. Abramyan

    (National Institute on Drug Abuse Intramural Research Program)

  • Sherry Lam

    (National Institute on Drug Abuse Intramural Research Program)

  • Matthew A. Boehm

    (National Institute on Drug Abuse Intramural Research Program)

  • Christina Ruiz

    (University of California)

  • Mitchell R. Farrell

    (University of California)

  • Andrea Moreno

    (Aarhus University)

  • Islam Mustafa Galal Faress

    (Aarhus University)

  • Niels Andersen

    (Aarhus University)

  • John Y. Lin

    (University of Tasmania)

  • Ruin Moaddel

    (National Institute on Aging Intramural Research Program)

  • Patrick J. Morris

    (National Center for Advancing Translational Sciences)

  • Lei Shi

    (National Institute on Drug Abuse Intramural Research Program)

  • David R. Sibley

    (National Institute of Neurological Disorders and Stroke Intramural Research Program)

  • Stephen V. Mahler

    (University of California)

  • Sadegh Nabavi

    (Aarhus University)

  • Martin G. Pomper

    (Department of Radiology Johns Hopkins School of Medicine)

  • Antonello Bonci

    (National Institute on Drug Abuse Intramural Research Program)

  • Andrew G. Horti

    (Department of Radiology Johns Hopkins School of Medicine)

  • Barry J. Richmond

    (National Institute of Mental Health Intramural Research Program)

  • Michael Michaelides

    (National Institute on Drug Abuse Intramural Research Program
    Johns Hopkins School of Medicine)

Abstract

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping.

Suggested Citation

  • Jordi Bonaventura & Mark A. G. Eldridge & Feng Hu & Juan L. Gomez & Marta Sanchez-Soto & Ara M. Abramyan & Sherry Lam & Matthew A. Boehm & Christina Ruiz & Mitchell R. Farrell & Andrea Moreno & Islam , 2019. "High-potency ligands for DREADD imaging and activation in rodents and monkeys," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12236-z
    DOI: 10.1038/s41467-019-12236-z
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    Cited by:

    1. Marie A. Labouesse & Maria Wilhelm & Zacharoula Kagiampaki & Andrew G. Yee & Raphaelle Denis & Masaya Harada & Andrea Gresch & Alina-Măriuca Marinescu & Kanako Otomo & Sebastiano Curreli & Laia Serrat, 2024. "A chemogenetic approach for dopamine imaging with tunable sensitivity," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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