Oral application of clozapine-N-oxide using the micropipette-guided drug administration (MDA) method in mouse DREADD systems
dc.contributor.author
Schalbetter, Sina M.
dc.contributor.author
Mueller, Flavia S.
dc.contributor.author
Scarborough, Joseph
dc.contributor.author
Richetto, Juliet
dc.contributor.author
Weber-Stadlbauer, Ulrike
dc.contributor.author
Meyer, Urs
dc.contributor.author
Notter, Tina
dc.date.accessioned
2021-03-15T07:42:13Z
dc.date.available
2021-03-13T04:34:14Z
dc.date.available
2021-03-15T07:42:13Z
dc.date.issued
2021-03
dc.identifier.issn
0093-7355
dc.identifier.other
10.1038/s41684-021-00723-0
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/474243
dc.description.abstract
The designer receptor exclusively activated by designer drugs (DREADD) system is one of the most widely used chemogenetic techniques to modulate the activity of cell populations in the brains of behaving animals. DREADDs are activated by acute or chronic administration of their ligand, clozapine-N-oxide (CNO). There is, however, a current lack of a non-invasive CNO administration technique that can control for drug timing and dosing without inducing substantial distress for the animals. Here, we evaluated whether the recently developed micropipette-guided drug administration (MDA) method, which has been used as a non-invasive and minimally stressful alternative to oral gavages, may be applied to administer CNO orally to activate DREADDs in a dosing- and timing-controlled manner. Unlike standard intraperitoneal injections, administration of vehicle substances via MDA did not elevate plasma levels of the major stress hormone, corticosterone, and did not attenuate exploratory activity in the open field test. At the same time, however, administration of CNO via MDA or intraperitoneally was equally efficient in activating hM3DGq-expressing neurons in the medial prefrontal cortex, as evident by time-dependent increases in mRNA levels of neuronal immediate early genes (cFos, Arc and Zif268) and cFos-immunoreactive neurons. Compared to vehicle given via MDA, oral administration of CNO via MDA was also found to potently increase locomotor activity in mice that express hM3DGq in prefrontal neurons. Taken together, our study confirms the effectiveness of CNO given orally via MDA and provides a novel method for non-stressful, yet well controllable CNO treatments in mouse DREADD systems.
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
dc.title
Oral application of clozapine-N-oxide using the micropipette-guided drug administration (MDA) method in mouse DREADD systems
en_US
dc.type
Journal Article
dc.date.published
2021-02-22
ethz.journal.title
Lab Animal
ethz.journal.volume
50
en_US
ethz.journal.issue
3
en_US
ethz.pages.start
69
en_US
ethz.pages.end
75
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
ethz.publication.status
published
en_US
ethz.relation.isPartOf
10.3929/ethz-b-000511874
ethz.date.deposited
2021-03-13T04:34:27Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2021-03-15T07:42:26Z
ethz.rosetta.lastUpdated
2024-02-02T13:17:38Z
ethz.rosetta.versionExported
true
ethz.COinS
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Journal Article [133574]