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Sleep. 2012 Jan 1;35(1):103-11. doi: 10.5665/sleep.1596.

Effects of GF-015535-00, a novel α1 GABA A receptor ligand, on the sleep-wake cycle in mice, with reference to zolpidem.

Author information

1
Integrative Physiology of Brain Arousal Systems, Lyon Neuroscience Research Center, INSERM U1028-CNRS UMR 5292, Faculty of Medicine, Claude Bernard University, 8 Avenue Rockefeller, Lyon Cedex 08, France.

Abstract

STUDY OBJECTIVES:

Novel, safe, and efficient hypnotic compounds capable of enhancing physiological sleep are still in great demand in the therapy of insomnia. This study compares the sleep-wake effects of a new α1 GABA(A) receptor subunit ligand, GF-015535-00, with those of zolpidem, the widely utilized hypnotic compound.

METHODS:

Nine C57Bl6/J male mice were chronically implanted with electrodes for EEG and sleep-wake monitoring. Each mouse received 3 doses of GF-015535-00 and zolpidem. Time spent in sleep-wake states and cortical EEG power spectra were analyzed.

RESULTS:

Both zolpidem and GF-015535-00 prominently enhanced slow wave sleep and paradoxical sleep in the mouse. However, as compared with zolpidem, GF-015535-00 showed several important differences: (1) a comparable sleep-enhancing effect was obtained with a 10 fold smaller dose; (2) the induced sleep was less fragmented; (3) the risk of subsequent wake rebound was less prominent; and (4) the cortical EEG power ratio between slow wave sleep and wake was similar to that of natural sleep and thus compatible with physiological sleep.

CONCLUSION:

The characteristics of the sleep-wake effects of GF-015535-00 in mice could be potentially beneficial for its use as a therapeutic compound in the treatment of insomnia. Further investigations are required to assess whether the same characteristics are conserved in other animal models and humans.

KEYWORDS:

Zolpidem; insomnia; mouse; sleep fragmentation; α1 GABAA receptor

PMID:
22215924
PMCID:
PMC3242675
DOI:
10.5665/sleep.1596
[Indexed for MEDLINE]
Free PMC Article

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