ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1596813
Synergistic effects of combined hypnotic drugs on sleep in mice
Provisionally accepted
- 1College of Life Science and Technology, Gansu Agricultural University, Lanzhou, Gansu Province, China
- 2State Key Laboratory of NBC Protection for Civilian, Beijing, China
- 3Department of Human Anatomy, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China
- 4Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, China
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Study Objectives: To investigate the interaction and potential mechanisms of the combined administration of dexmedetomidine (DMED) and eszopiclone (ESZ) on sleep in mice. Methods: The effects of DMED, ESZ and the combination of the two drugs on the sleep status of mice were investigated by using the loss of righting reflex (LORR) as an indicator, the sleep-related parameters were recorded, and the interactions of the combination of DMED and ESZ on sleep were determined by isobolographic analysis. The effects of DMED and ESZ on sleep structure, the regulation of c-Fos protein expression in the ventrolateral preoptic area (VLPO) and the tuberomammillary nucleus (TMN) and the regulation of neurotransmitter levels were further investigated by combining electroencephalogram/electromyogram (EEG/EMG) sleep phase analysis, c-Fos immunofluorescence, and neurotransmitter content measurements in the brain. Results: Isobolographic analysis demonstrated that the combination of DMED and ESZ had a synergistic effect on sleep in mice. The duration of non-rapid eye movement (NREM) sleep was significantly prolonged; the number of c-Fos positive neurons increased in the VLPO and decreased in the TMN; the levels of excitatory neurotransmitters were reduced, while the levels of inhibitory neurotransmitters were elevated. Conclusion: This study reveals that the combination of DMED and ESZ exerts a synergistic effect on sleep in mice. The underlying mechanism may involve the prolongation of NREM sleep, modulation of neuronal activity in the brain regions of VLPO and TMN, as well as alteration in the levels of brain neurotransmitters.
Keywords: Sleep, hypnotics, Dexmedetomidine, Eszopiclone, combination, Synergistic effects
Received: 20 Mar 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Bai, Wang, Wu, Yin, Liu, Gao and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuan Gao, College of Life Science and Technology, Gansu Agricultural University, Lanzhou, Gansu Province, China
Yunyang Song, State Key Laboratory of NBC Protection for Civilian, Beijing, China
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