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

Citation

Bonaventura, J and Eldridge, MAG and Hu, F and Gomez, JL and Sanchez-Soto, M and Abramyan, AM and Lam, S and Boehm, MA and Ruiz, C and Farrell, MR and Moreno, A and Faress, IMG and Andersen, N and Lin, JY and Moaddel, R and Morris, PJ and Shi, L and Sibley, DR and Mahler, SV and Nabavi, S and Pomper, MG and Bonci, A and Horti, AG and Richmond, BJ and Michaelides, M, High-potency ligands for DREADD imaging and activation in rodents and monkeys, Nature communications, 10, (1) Article 4627. ISSN 2041-1723 (2019) [Refereed Article]


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Copyright 2019 The Author(s) Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/s41467-019-12236-z

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

Item Details

Item Type:Refereed Article
Keywords:Chemogenetics, optogenetics
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the environmental sciences
UTAS Author:Lin, JY (Dr John Lin)
ID Code:135335
Year Published:2019
Web of Science® Times Cited:60
Deposited By:Medicine
Deposited On:2019-10-14
Last Modified:2022-08-23
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