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

Authors

Subhashis Banerjee, The Scripps Research Institute
Yongjun Wang, Saint Louis University School of Medicine
Laura A. Solt, The Scripps Research Institute
Kristine Griffett, Saint Louis University School of Medicine
Melissa Kazantzis, The Scripps Research Institute
Ariadna Amador, The Scripps Research Institute
Bahaa M. El-Gendy, The Scripps Research Institute
Salvador Huitron-Resendiz, The Scripps Research Institute
Amanda J. Roberts, The Scripps Research Institute
Youseung Shin, The Scripps Research Institute
Theodore M. Kamenecka, The Scripps Research Institute
Thomas P. Burris, Saint Louis University School of Medicine

Document Type

Article

Date of this Version

2014

Citation

NATURE COMMUNICATIONS | 5:5759

Comments

Copyright 2014 Macmillan Publishers Limited.

DOI: 10.1038/ncomms6759

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.