Eye-Drops for Activation of DREADDs.

Eye-Drops for Activation of DREADDs.
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DOI:
10.3389/fncir.2017.00093
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发表时间:
2017
影响因子:
3.5
通讯作者:
Hattar S
Hattar S
中科院分区:
医学3区
文献类型:
--
作者:
Keenan WT;Fernandez DC;Shumway LJ;Zhao H;Hattar S

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设计物药物特异性激活的设计物受体(DREADDs)是调控和理解神经回路的重要工具。根据所使用的DREADD系统,在一定剂量的DREADD激动剂氯氮平- n -氧化物(CNO)后,可以在体内激活或抑制DREADD靶向神经元。因为DREADD实验经常涉及行为分析,所以CNO传递的方法很重要。目前,最常见的给药方式是腹腔注射。IP注射是一种既快速又可靠的技术,但当需要多次注射时,它会带来痛苦和压力。我们寻求一种替代的CNO递送模式,它将保持IP注射的速度和可靠性,而不会产生侵入性。在这里,我们证明CNO可以通过滴眼液有效地局部递送。滴眼液能有效激活大脑和外周组织中表达dreadd的神经元,其剂量与IP注射相同。滴眼液提供了一种更简单、侵入性更小、压力更小的激活体内dreadd的方法。
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 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.
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