中国药理学与毒理学杂志2024，Vol.38Issue(2)：81-88,8.DOI:10.3867/j.issn.1000-3002.2024.02.001
唑吡坦对低压低氧致失眠模型小鼠的镇静催眠作用
Sedative and hypnotic effects of zolpidem on insomnia model mice induced by hypoxia
摘要
Abstract
OBJECTIVE To study the sedative and hypnotic effects of zolpidem and the content of amino acid neurotransmitters in the thalamus and hypothalamus after treatment with zolpidem.METHODS Experiments on the loss of righting reflex(LORR)induced by the upper-threshold dose pentobarbital sodium(50 mg·kg-1,ip)were conducted to establish a hypoxic insomnia model in mice by simulating an altitude of 5500 m.Based on this model,the synergistic effect of zolpidem(0.33,1,3,9 and 27 mg·kg-1,ip)and the subthreshold(20 mg·kg-1,ip)and upper-threshold pentobarbital sodium,as well as the sedative hypnotic effect of zolpidem(10,13,17,20,23,30 and 40 mg·kg-1,ip)were evaluated via the LORR in normoxic and hypoxic environments.One hour after ip given zolpidem,the levels of glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the thalamus and hypothalamus of mice in either environment were determined by the high-performance liquid chromatography(HPLC)with fluorescence detection.RESULTS One-day treatment with hypoxia significantly shortened the duration of LORR induced by the upper-threshold dose pentobarbital sodium.Compared with normoxia vehicle and hypoxia induced insomnia vehicle groups,zolpidem 9 and 27 mg·kg-1 significantly shortened the latency to LORR(P<0.01,P<0.05)and prolonged duration of LORR induced by subthreshold and upper-threshold pentobarbital sodi-um(P<0.01,P<0.05).The median effective dose(ED50)of LORR induced by zolpidem was 16.21 and 20.55 mg·kg-1 in normoxic and hypoxic environments,respectively.The results of neurotransmitter level detection showed that Glu contents in the thalamus and hypothalamus and the ratio of Glu/GABA in the hypothalamus were decreased after treatment with zolpidem 40 mg·kg-1 in a normoxic environment(P<0.01,P<0.05).Compared with the normoxia control group,Glu content and the ratio of Glu/GABA in the hypothalamus were significantly increased after treatment with hypoxia(P<0.01,P<0.05),and zolpidem 40 mg·kg-1 could reverse their elevation.CONCLUSION The sedative-hypnotic effect of zolpidem is weakened in a hypoxic environment,and the effect of zolpidem on the levels of Glu and GABA in the hypothalamus may play an important role in the sedative-hypnotic effect of zolpidem.关键词
低压低氧/唑吡坦/翻正反射/谷氨酸/γ-氨基丁酸Key words
hypoxia/zolpidem/righting reflex/glutamic acid/γ-aminobutyric acid分类
医药卫生引用本文复制引用
梁欢欢,许琳,俞纲,苏瑞斌,李明媛..唑吡坦对低压低氧致失眠模型小鼠的镇静催眠作用[J].中国药理学与毒理学杂志,2024,38(2):81-88,8.基金项目
天津市教委"十三五综投"项目(2018KJ124) （2018KJ124）
天津市透明质酸应用研究企业重点实验室开放基金(KTRDHA-Y201906) Tianjin Education Commission"13th Five-Year Comprehensive Investment"project(2018KJ124) （KTRDHA-Y201906）
and Tianjin Laboratory of Hyaluronic Acid Applied Research Enterprise Open Fund(KTRDHA-Y201906) （KTRDHA-Y201906）
