Article Dans Une Revue (Data Paper) Sleep Année : 2012

Effects of GF-015535-00, a Novel α1 GABAA Receptor Ligand, on the Sleep-Wake Cycle in Mice, with Reference to Zolpidem

Résumé

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.

Dates et versions

hal-04799440 , version 1 (22-11-2024)

Identifiants

Citer

Christelle Anaclet, Mei Zhang, Chunmei Zhao, Colette Buda, Laurent Seugnet, et al.. Effects of GF-015535-00, a Novel α1 GABAA Receptor Ligand, on the Sleep-Wake Cycle in Mice, with Reference to Zolpidem. Sleep, 2012, 35 (1), pp.103-111. ⟨10.5665/sleep.1596⟩. ⟨hal-04799440⟩
44 Consultations
0 Téléchargements

Altmetric

Partager

  • More