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Nat Commun. 2014 Dec 23;5:5759. doi: 10.1038/ncomms6759.

Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour.

Author information

1
Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33458, USA.
2
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, Missouri 63104, USA.
3
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California 92037, USA.

Abstract

Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the potential to directly modulate the endogenous circadian rhythm and treat diseases associated with clock dysfunction. Here we demonstrate that synthetic ligands targeting a key component of the mammalian clock, the nuclear receptors REV-ERBα and β, regulate sleep architecture and emotional behaviour in mice. REV-ERB agonists induce wakefulness and reduce REM and slow-wave sleep. Interestingly, REV-ERB agonists also reduce anxiety-like behaviour. These data are consistent with increased anxiety-like behaviour of REV-ERBβ-null mice, in which REV-ERB agonists have no effect. These results indicate that pharmacological targeting of REV-ERB may lead to the development of novel therapeutics to treat sleep disorders and anxiety.

PMID:
25536025
PMCID:
PMC4495958
DOI:
10.1038/ncomms6759
[Indexed for MEDLINE]
Free PMC Article

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