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Front. Neural Circuits | doi: 10.3389/fncir.2017.00093

Eye-drops for activation of DREADDs

  • 1Biology Department, Johns Hopkins University, United States
  • 2National Institute of Mental Health (NIMH), National Institutes of Health (NIH), United States
  • 3National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), United States

Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are an important tool for modulating and understanding neural circuits. Depending on the DREADD system used, DREADD-targeted neurons can be activated or repressed in vivo following a dose of the DREADD agonist clozapine-n-oxide (CNO). Because DREADD experiments often involve behavioral assays, the method of CNO delivery is important. Currently, the most common delivery method is intraperitoneal (IP) injection. IP injection is both a fast and reliable technique, but it is painful and stressful particularly when many injections are required. We sought an alternative CNO delivery paradigm, which would retain the speed and reliability of IP injections without being as invasive. Here we show that CNO can be effectively delivered topically via eye-drops. Eye-drops robustly activated DREADD-expressing neurons in the brain and peripheral tissues and does so at the same dosages as IP injection. Eye-drops provide an easier, less invasive and less stressful method for activating DREADDs in vivo.

Keywords: chemogenetics, DREADD, Behavior, neural circuit, Clozapine N-oxide

Received: 11 Jul 2017; Accepted: 09 Nov 2017.

Edited by:

Michael Nitabach, Yale School of Medicine, Yale University, United States

Reviewed by:

Ralph DiLeone, Yale University, United States
Thomas L. Kash, University of North Carolina at Chapel Hill, United States  

Copyright: © 2017 Keenan, Fernandez, Shumway, Zhao and Hattar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. William T. Keenan, Johns Hopkins University, Biology Department, Baltimore, 21218, Maryland, United States,