Comparison of benzodiazepines and the non-benzodiazepine agents zolpidem and zaleplon with respect to anxiolytic action as measured by increases in hypertonic NaCl-solution drinking in rats.
Comparison of benzodiazepines and the non-benzodiazepine agents zolpidem and zaleplon with respect to anxiolytic action as measured by increases in hypertonic NaCl-solution drinking in rats.
复制标题
通过增加大鼠高渗氯化钠溶液饮用量来测量苯二氮卓类药物与非苯二氮卓类药物唑吡坦和扎来普隆的抗焦虑作用的比较。
DOI：
10.1007/s002139900354
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发表时间：
2000
影响因子：
3.4
通讯作者：
Falk,JL
中科院分区：
文献类型：
--
作者：
Lobarinas,E;Falk,JL
依据：在先前的研究中，给缺水大鼠提供高渗1.5% NaCl溶液饮用，当用已知在人类中具有抗焦虑作用的药物治疗时，显示摄入量增加。本研究探讨了两个非benzodiazepines（非BZ）的镇静催眠药，唑吡坦和扎来普隆，并将它们与三个传统的BZs.Objectives：虽然许多研究证实，治疗具有镇静催眠和抗焦虑作用的BZs也产生急性增加动物的食物和液体摄入，唑吡坦产生了相互矛盾的结果。为了帮助解决这个问题，我们比较了三个BZ与唑吡坦和扎来普隆方面，他们的行动，在增加摄入的1.5%NaCl溶液在water-deprived rates.Methods：大鼠适应水剥夺时间表，允许每天饮用1小时。每周一次或两次，在饮水期间用1.5%NaCl溶液代替水，并且在饮水前15分钟，通过管饲法（p.o.）描述唑吡坦、扎来普隆、阿普唑仑、氯硝西泮和利氮卓的剂量-效应关系。然后，重新确定唑吡坦的剂量-效应关系。第二个研究与两个组，使用唑吡坦和氯硝西泮，探讨是否以下的药物的剂量-效应测定的第二次测定影响第二关系，以及是否剂量-效应测定的任何代理影响的结果的第二代理investigated.Results：所有代理产生剂量相关的增加，在1.5%NaCl溶液的摄入，除了第一唑吡坦测定在第一项研究。在第二项研究中，所有的测定都产生了剂量相关的增加，没有迹象表明第一种药物的测定影响了第二种药物的测定。结论：BZ和非BZ药物探索产生了显着的剂量-效应关系，使用此程序，确认其抗焦虑药物之间的分类。第一项研究中唑吡坦的初始阴性结果可能表明该药物的抗焦虑作用不太可靠，尽管这不能归因于药物史。
Rationale:In previous studies, water-deprived rats offered hypertonic 1.5% NaCl solutions to drink showed increased intakes when treated with agents known to have anxiolytic action in humans. This study explored two non-benzodiazepine (non-BZ) sedative-hypnotic agents, zolpidem and zaleplon, and compared them with three traditional BZs.Objectives:Although many studies confirm that treatment with BZs possessing sedative-hypnotic and anxiolytic actions also produces acute increases in food and fluid ingestion in animals, zolpidem has yielded conflicting results. To help resolve this question, we compared three BZs with zolpidem and zaleplon with respect to their actions in increasing the ingestion of 1.5% NaCl solution in water-deprived rats.Methods:Rats were adapted to a water-deprivation schedule permitting drinking for 1 h daily. Once or twice each week, 1.5% NaCl solution was substituted for water during the drinking session and, 15 min pre-session, rats were given a drug or vehicle dose by gavage (p.o.) to delineate the dose–effect relationships for zolpidem, zaleplon, alprazolam, clonazepam, and chlordiazepoxide. Then, the dose–effect relationship for zolpidem was re-determined. A second study with two groups, using both zolpidem and clonazepam, explored whether following the dose–effect determination of a drug by a second determination affected the second relationship, and whether dose–effect determinations of either agent affected the results of the second agent investigated.Results:All agents yielded dose-related increases in 1.5% NaCl solution ingestion, except the first zolpidem determination in the first study. In the second study, all determinations yielded dose-related increases, with no indication that the set of determinations for the first agent affected those for the second agent.Conclusions:The BZ and non-BZ agents explored yielded significant dose–effect relationships using this procedure, confirming their classification among the anxiolytic agents. The initial negative result for zolpidem in the first study may indicate a less reliable anxiolytic action for this agent, although this could not be resolved as attributable to drug history.