Effect Of Acute Hypobaric Hypoxia On Efficacy And Safety Of Eszopiclone And Diazepam In Mice

Object: To assess the effects of acute hypobaric hypoxia on hypoxia on efficacy and safety ofeszopiclone and diazepam with the pentobarbital sodium-induced sleeping time, spontaneousactivity and learning and memory abilities.Methods:270mice were randomly divided into9groups by using two designs of2×3levelsfactorial,in which two factors are interventions (ESZ and0.9%sodium chloride,2levels),(DZ and0.9%sodium chloride,2levels) and hypobaric hypoxia (800m,3500m and6000m,3levels).Thepentobarbital sodium-induced sleeping test, the open field test and the Morris water maze testwere engaged to assess the effects of acute hypobaric hypoxia on sleeping time,spontaneousactivity and learning and memory ability with injecting of ESZ and DZ in mice.Results:1) In the study that effects of acute hypobaric hypoxia on efficacy and safety of ESZ inmice, the hypobaric hypoxia and drug have no interaction in the results of both the pentobarbitalsodium-induced sleeping test, the open field test and Morris water maze test(P>0.05). The time ofpentobarbital sodium-induced sleeping were longer in group of6000m than in the other twogroups, both the ESZ and NS groups (P<0.05);The time of pentobarbital sodium-induced sleepingof mice in the groups of ESZ in different hypobaric hypoxia were longer than in the groups of NSat relevant hypobaric hypoxia（800m:37.77±18.22min VS17.78±14.10min;3500m:37.02±13.67min VS15.09±12.46min;6000m:95.67±47.68minVS39.54±28.24min,P<0.05）. No significantdifference was found in the open field test between the ESZ and NS groups in the same hypobarichypoxia(P>0.05); while the mice in the hypobaric hypoxia of6000m in groups of ESZ and NSwere all decreased compared with the groups at800m after intraperitoneal injection the relevantdrugs6h (P<0.05&P<0.01). No significant difference was found in the learning and memoryability between the ESZ and NS groups in the same hypobaric hypoxia(P>0.05); while the mice atthe hypobaric hypoxia of6000m in groups of ESZ and NS were all decreased compared with thegroups at800m after intraperitoneal injection the relevant drugs6h (P<0.05&P<0.01).2) In thestudy that effects of acute hypobaric hypoxia on efficacy and safety of ESZ in mice, thehypobaric hypoxia and drug have interaction in the results of the pentobarbital sodium-inducedsleeping test, not of the open field test and Morris water maze test(P>0.05). The time ofpentobarbital sodium-induced sleeping were longer in group of6000m than in the other twogroups, both the DZ and NS groups (P<0.05); The time of pentobarbital sodium-induced sleepingof mice in the groups of DZ in different hypobaric hypoxia were longer than in the groups of NSat relevant hypobaric hypoxia （800m:70.43±48.26min VS17.78±14.10min;3500m:61.63±43.46min VS15.09±12.46min;6000m:159.16±33.27min VS39.54±28.24min,P<0.05）.No significant difference was found in the open field test between the DZ and NSgroups in the same hypobaric hypoxia(P>0.05)，except for the of mice in hypobaric hypoxia of6000m;while the mice in the hypobaric hypoxia of6000m in groups of ESZ and NS were alldecreased compared with the groups of800m after intraperitoneal injection the relevant drugs6h(P<0.05&P<0.01). No significant difference was found in the learning and memory abilitybetween the DZ and NS groups in the same hypobaric hypoxia(P>0.05); while the mice in thehypobaric hypoxia of6000m in groups of DZ and NS were all decreased compared with thegroups in the hypobaric hypoxia of800m after intraperitoneal injection the relevant drugs6h (P<0.05&P<0.01).Conclusion:1)Hypobaric hypoxia of6000m may prolong the sleep time induced bypentobarbital sodium and reduce the spontaneous activities and the learning and memoryabilities.ESZ may prolong pentobarbital sodium-induced sleeping time with no influence with thespontaneous activity in mice exposed to acute hypobaric hypoxia.2)Hypobaric hypoxia of6000mmay prolong the sleep time induced by pentobarbital sodium and reduce the rearing and thelearning and memory abilities.DZ may prolong pentobarbital sodium-induced sleeping time withno influence with the spontaneous activity in mice exposed to acute hypobaric hypoxia.