Roles of extrasynaptic GABAA receptors in sleep-promoting effect of zolpidem
10.3867/j.issn.1000-3002.2025.07785
- VernacularTitle:含δ-亚基的突触外γ-氨基丁酸A型受体在唑吡坦促睡眠效应中的作用
- Author:
Xiaowei JIANG
1
;
Gang YU
;
Ruibin SU
Author Information
1. 南京中医药大学,江苏 南京 210023;军事医学研究院神经精神药理学北京市重点实验室,北京 100850
- Publication Type:Journal Article
- Keywords:
zolpidem;
extrasynaptic GABAA receptor;
electroencephalography;
slow-wave activity
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(6):412-418
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the role of δ-subunit-containing extrasynaptic γ-aminobutyric acid type A receptor(GABAAR)in sleep-promoting effects of zolpidem(ZPD).METHODS ①C57BL/6J mice were implanted with skull electrodes and allowed postoperative recovery of seven days.Groups of mice were intraperitoneally(ip)administered with ZPD at 0(vehicle control),2.5,5 and 10 mg·kg-1.Cortical electroencephalography(EEG)was recorded to analyze latencies of non-rapid eye movement(NREM)and rapid eye movement(REM)sleep,the percentage of wakefulness,NREM and REM sleep,sleep architecture(the proportion of NREM and REM sleep in sleep,number of times and mean duration of NREM and REM sleep,microarousals and short awakenings),EEG power density and slow-wave activity(SWA,0.5-4 Hz)during NREM sleep.② Wild-type(WT)and δ-subunit knockout(δ-KO)mice were ip administered with vehicle or ZPD 10 mg·kg-1 before cortical EEG parameters were ana-lyzed to compare ZPD effects between genotypes.RESULTS ①Compared with the vehicle,ZPD 2.5,5 and 10 mg·kg-1 significantly shortened NREM sleep latency.ZPD 5 and 10 mg·kg-1 markedly reduced wakefulness and increased NREM sleep time.ZPD 2.5 and 10 mg·kg-1 increased NREM sleep episode frequency while ZPD 10 mg·kg-1 elevated brief awakening frequency.REM sleep remained unchanged.②In δ-KO mice,ZPD 10 mg·kg-1 significantly shortened NREM sleep latency compared with WT mice,but its effects on increasing short awakenings and suppressing SWA were abolished.Zolpidem showed no significant differences in the proportion of each sleep phase,the average duration of NREM sleep,and the frequency of REM sleep in KO mice compared to its effects on WT mice.CONCLUSION ZPD-induced sleep fragmentation and reduced sleep depth are mediated by δ-subunit-containing extra-synaptic GABAAR,whereas its shortening of NREM sleep latency is independent of this receptor subtype.
