Biology Department, Johns Hopkins University, Baltimore, MD, United States.
National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States.
Front Neural Circuits. 2017 Nov 23;11:93. doi: 10.3389/fncir.2017.00093. eCollection 2017.
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are an important tool for modulating and understanding neural circuits. Depending on the DREADD system used, DREADD-targeted neurons can be activated or repressed following a dose of the DREADD agonist clozapine--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 .
设计者受体专门被设计者药物激活（DREADDs）是调节和了解神经回路的重要工具。根据使用的 DREADD 系统，DREADD 靶向神经元可以在给予 DREADD 激动剂氯氮平-氧化物（CNO）后被激活或抑制。由于 DREADD 实验通常涉及行为测定，因此 CNO 的给药方法很重要。目前，最常用的给药方法是腹腔内（IP）注射。IP 注射既快速又可靠，但当需要多次注射时，它是痛苦和有压力的。我们寻求替代的 CNO 给药范式，它将保留 IP 注射的速度和可靠性，而不会那么具有侵入性。在这里，我们表明 CNO 可以通过滴眼剂有效地局部递送。滴眼剂可在大脑和外周组织中强有力地激活 DREADD 表达的神经元，并且其剂量与 IP 注射相同。滴眼剂提供了一种更简单、侵入性更小、压力更小的激活 DREADD 的方法。
