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阶梯试验:抗焦虑药非特异性的一些证据。

The staircase test: some evidence of nonspecificity for anxiolytics.

作者信息

Pollard G T, Howard J L

出版信息

Psychopharmacology (Berl). 1986;89(1):14-9. doi: 10.1007/BF00175182.

DOI:10.1007/BF00175182
PMID:2874582
Abstract

In the staircase test, a naive mouse is placed in a Plexiglas chamber containing a five-step staircase, and the number of rearings and steps climbed are recorded for 3 min. A claim for drug-class specificity has been made because conventional anxiolytics reduced rearings at doses that did not reduce steps climbed, while non-anxiolytics affected both measures in parallel. In the present study chlordiazepoxide, meprobamate, and ethanol registered the expected true positive effect by reducing rearings at doses that did not reduce steps climbed. Nicotine, which has some clinical anxiolytic action, registered a small true positive. The benzodiazepine anxiolytic alprazolam reduced both measures, a false negative, although it reduced rearings more than steps climbed. The putative novel anxiolytics CGS 9896, ketanserine, and tracazolate registered negatives, as did the known clinical anxiolytic buspirone. The non-anxiolytics phencyclidine and phenacetin registered true negatives, but morphine registered a clear false positive. The anxiogenics FG 7142 and pentylenetetrazol produced no significant effects. Because of the equivocal false negative for alprazolam, the clear false negative for buspirone, and the clear false positive for morphine, we concluded that the test lacks the degree of therapeutic-class specificity previously proposed but may still be useful in basic research.

摘要

在阶梯试验中,将一只未经处理的小鼠置于一个装有五步阶梯的有机玻璃箱中,记录其3分钟内的竖尾次数和攀爬的步数。有人提出该试验具有药物类别特异性,因为传统抗焦虑药在不减少攀爬步数的剂量下能减少竖尾次数,而非抗焦虑药则同时影响这两项指标。在本研究中,氯氮卓、甲丙氨酯和乙醇通过在不减少攀爬步数的剂量下减少竖尾次数,显示出预期的真阳性效应。具有一定临床抗焦虑作用的尼古丁显示出小的真阳性。苯二氮卓类抗焦虑药阿普唑仑减少了两项指标,这是一个假阴性结果,尽管它减少竖尾次数的程度大于减少攀爬步数的程度。假定的新型抗焦虑药CGS 9896、酮色林和曲卡唑显示为阴性,已知的临床抗焦虑药丁螺环酮也是如此。非抗焦虑药苯环利定和非那西丁显示为真阴性,但吗啡显示出明显的假阳性。致焦虑剂FG 7142和戊四氮未产生显著影响。由于阿普唑仑存在不明确的假阴性、丁螺环酮明确的假阴性以及吗啡明确的假阳性,我们得出结论,该试验缺乏先前提出的治疗类别特异性程度,但在基础研究中可能仍有用处。

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