ArticleeLife2023
Effects of clozapine-N-oxide and compound 21 on sleep in laboratory mice.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Article
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- Disrupted temperature-sleep coupling mechanism in a Dravet syndrome mouse model.Nature communications · 2026Article
- Coordination of distinct sources of excitatory inputs enhances motion selectivity in the mouse visual thalamus.Neuron · 2025Article
- Neuro-immune regulation of sepsis-associated delirium via the PBN-CeA-spleen axis.Journal of neuroinflammation · 2025Article
- Sex-dependent modulation of behavioral allocation via ventral tegmental area-nucleus accumbens shell circuitry.NeuroImmune pharmacology and therapeutics · 2025Article
- Chronic Chemogenetic Activation of Astrocytes in the Murine Mesopontine Region Leads to Disturbances in Circadian Activity and Movement.International journal of molecular sciences · 2025Article
- Chronic chemogenetic slow-wave-sleep enhancement in mice.bioRxiv : the preprint server for biology · 2025Article
- Mesolimbic dopamine neurons drive infradian rhythms in sleep-wake and heightened activity state.Science advances · 2025Article
- Glial cells undergo rapid changes following acute chemogenetic manipulation of cortical layer 5 projection neurons.Communications biology · 2024Article
- Ventral subiculum promotes wakefulness through several pathways in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation.Nature communications · 2024Article
- Neuronal PAS domain 1 identifies a major subpopulation of wakefulness-promoting GABAergic neurons in the basal forebrain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chemogenetic activation of astrocytes modulates sleep-wakefulness states in a brain region-dependent manner.Sleep advances : a journal of the Sleep Research Society · 2024Article
- Clozapine N-oxide, compound 21, and JHU37160 do not influence effortful reward-seeking behavior in mice.Psychopharmacology · 2024Article
- Advanced neurobiological tools to interrogate metabolism.Nature reviews. Endocrinology · 2023Review
- Prefrontal Cortical Regulation of REM Sleep.Research square · 2023Article
- Prefrontal cortical regulation of REM sleep.Nature neuroscience · 2023Article
- Somatostatin neurons in prefrontal cortex initiate sleep-preparatory behavior and sleep via the preoptic and lateral hypothalamus.Nature neuroscience · 2023Article
- Parvalbumin neurons in the anterior nucleus of thalamus control absence seizures.Epilepsia open · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 5 countries.
Funding
Abstract
Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remote control of targeted cell populations using chemical actuators that bind to modified receptors. Despite the popularity of DREADDs in neuroscience and sleep research, potential effects of the DREADD actuator clozapine-N-oxide (CNO) on sleep have never been systematically tested. Here, we show that intraperitoneal injections of commonly used CNO doses (1, 5, and 10 mg/kg) alter sleep in wild-type male laboratory mice. Using electroencephalography (EEG) and electromyography (EMG) to analyse sleep, we found a dose-dependent suppression of rapid eye movement (REM) sleep, changes in EEG spectral power during non-REM (NREM) sleep, and altered sleep architecture in a pattern previously reported for clozapine. Effects of CNO on sleep could arise from back-metabolism to clozapine or binding to endogenous neurotransmitter receptors. Interestingly, we found that the novel DREADD actuator, compound 21 (C21, 3 mg/kg), similarly modulates sleep despite a lack of back-metabolism to clozapine. Our results demonstrate that both CNO and C21 can modulate sleep of mice not expressing DREADD receptors. This implies that back-metabolism to clozapine is not the sole mechanism underlying side effects of chemogenetic actuators. Therefore, any chemogenetic experiment should include a DREADD-free control group injected with the same CNO, C21, or newly developed actuator. We suggest that electrophysiological sleep assessment could serve as a sensitive tool to test the biological inertness of novel chemogenetic actuators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.