111 — Eye-Drops for Activation of DREADDs

There are many techniques for manipulating neural behavior through the use of pharmaceuticals or other chemicals. One such method that does not require is the injection of clozapine-N-oxide (CNO), a molecule that activates a non-native class of receptors known as DREADDs, or Designer Receptors Exclusively Activated by Designer Drugs. The most common form of CNO-delivery is currently injection, but this can be a stressful event for subjects. This is particularly an issue for studies about stress, but naturally a painful or stressful procedure should always be avoided if possible.

This paper presents a method of DREADD-agonist delivery that uses eyedrops as an introduction strategy. Using a pipette, small doses of CNO suspended in saline were dripped into mouse eyes. The CNO, which circulated in blood, was still delivered to the neural tissue in CNS even though it was applied noninvasively.

This was measured by watching pupil constriction, with DREADDs inserted in retinal ganglion cells responsible for driving this constriction response. Even smaller doses of CNO were required to drive the same response than had it been applied via intraperitoneal injection.

The same experiment was carried out in mice expressing the DREADDs in hippocampal neurons, with a similar result: CNO, delivered by eyedrop, is able to permeate the blood-brain barrier and activate central nervous system neurons.

This is great news both for experimenters — whose protocols can be less tainted with stress responses, and who now can spend less on injection protocols — as well as the mice, who maybe don’t get intraperitoneal injections as much anymore.