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Eye-Drops for Activation of DREADDs.

William T Keenan1, Diego C Fernandez1,2, Lukas J Shumway3

  • 1Biology Department, Johns Hopkins University, Baltimore, MD, United States.

Frontiers in Neural Circuits
|December 9, 2017
PubMed
Summary

Topical eye-drops offer a less invasive method for administering clozapine-N-oxide (CNO) to activate Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neurons. This eye-drop approach provides a faster, more reliable, and less stressful alternative to traditional injections for DREADD research.

Keywords:
DREADDbehaviorchemogeneticsclozapine-N-oxideneural circuit

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are crucial for neural circuit modulation.
  • Clozapine-N-oxide (CNO) is the standard agonist for activating DREADDs in vivo.
  • Intraperitoneal (IP) injection is the common CNO delivery method but is invasive and stressful.

Purpose of the Study:

  • To identify a less invasive and equally effective method for CNO delivery.
  • To evaluate topical eye-drops as an alternative CNO administration route.

Main Methods:

  • DREADD-expressing neurons were activated using CNO delivered via eye-drops.
  • The efficacy of eye-drop delivery was compared to IP injection.
  • Activation of DREADD-expressing neurons in the brain and peripheral tissues was assessed.

Main Results:

  • Topical eye-drops effectively activated DREADD-expressing neurons.
  • The dosage required for eye-drop activation was comparable to IP injection.
  • Eye-drop delivery proved to be a robust method for CNO administration.

Conclusions:

  • Topical eye-drops provide an easier, less invasive, and less stressful method for activating DREADDs in vivo.
  • This novel delivery method maintains the speed and reliability of IP injections.
  • Eye-drop administration represents a significant advancement for DREADD-based research.