Inhibition of Orexin Signaling Promotes Sleep Yet Preserves Salient Arousability in Monkeys.

ABSTRACT:

Study objectives

In addition to enhancing sleep onset and maintenance, a desirable insomnia therapeutic agent would preserve healthy sleep's ability to wake and respond to salient situations while maintaining sleep during irrelevant noise. Dual orexin receptor antagonists (DORAs) promote sleep by selectively inhibiting wake-promoting neuropeptide signaling, unlike global inhibition of central nervous system excitation by gamma-aminobutyric acid (GABA)-A receptor (GABAaR) modulators. We evaluated the effect of DORA versus GABAaR modulators on underlying sleep architecture, ability to waken to emotionally relevant stimuli versus neutral auditory cues, and performance on a sleepiness-sensitive cognitive task upon awakening.

Methods

DORA-22 and GABAaR modulators (eszopiclone, di

SUBMITTER: Tannenbaum PL 

PROVIDER: S-EPMC4763356 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature