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Abstract

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popularchemogenetic technology for manipulation of neuronal activity in uninstrumented awakeanimals with potential for human applications as well. The prototypical DREADD agonistclozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult toapply in basic and translational applications. Here we report the development of two novelDREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emissiontomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 andJHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allowsfor DREADD detection in locally-targeted neurons, and at their long-range projections,enabling noninvasive and longitudinal neuronal projection mapping

Item Type:	Article
Authors/Creators:	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
Keywords:	Chemogenetics, optogenetics
Journal or Publication Title:	Nature communications
Publisher:	Nature Publishing Group
ISSN:	2041-1723
DOI / ID Number:	https://doi.org/10.1038/s41467-019-12236-z
Copyright Information:	Copyright 2019 The Author(s)Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)https://creativecommons.org/licenses/by/4.0/
Related URLs:	UTAS Profile: Lin, JY
Item Statistics:	View statistics for this item

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