Porsolt R D, Chermat R, Lenègre A, Avril I, Janvier S, Stéru L
I.T.E.M.-LABO, Kremlin-Bicêtre, France.
Arch Int Pharmacodyn Ther. 1987 Jul;288(1):11-30.
Mice, when suspended by the tail, will alternate between active attempts to escape and immobility. A specially developed computerized device (ITEMATIC-TST) automatically measures the duration of immobility of 6 mice at one time and at the same time provides a measure of the energy expended by each animal, the power of the movements. Use of these 2 parameters enables activity profiles to be generated which can distinguish different classes of psychotropic activity. Immobility is decreased by antidepressants and psychostimulants, but increased by neuroleptics and minor tranquillizers. Minor tranquillizers can be distinguished from neuroleptics in that they decrease the power of the movements, whereas neuroleptics are without effect on this parameter. The present experiments were undertaken to see whether the activity profiles generated in this procedure could indeed be useful for primary psychotropic screening. Eighteen compounds, including antidepressants, neuroleptics, minor tranquillizers, sedative/hypnotics, dopaminergic stimulants and 3 dummy compounds were first submitted to a shortened primary observation procedure for dose finding and were then investigated at 2 doses in the automated tail suspension test. All experiments were conducted blind. The results obtained largely confirm the activity profiles already reported in this test and show that the combined use of primary observation and the automated tail suspension test permit the unambiguous identification of the pharmacological activity of 15 of the compounds tested with tentative identification of the 3 remaining compounds.
小鼠被尾巴悬吊时,会在积极尝试逃脱和静止不动之间交替。一种专门开发的计算机化装置(ITEMATIC-TST)可同时自动测量6只小鼠的静止不动时间,并同时提供每只动物所消耗能量及运动功率的测量值。利用这两个参数能够生成活动图谱,从而区分不同类别的精神活性。抗抑郁药和精神兴奋药可减少静止不动时间,而抗精神病药和弱安定药则会增加静止不动时间。弱安定药与抗精神病药的区别在于,前者会降低运动功率,而后者对该参数没有影响。进行本实验是为了观察在此程序中生成的活动图谱是否确实可用于初步精神药物筛选。首先将18种化合物,包括抗抑郁药、抗精神病药、弱安定药、镇静/催眠药、多巴胺能兴奋剂和3种虚拟化合物,进行缩短的初步观察程序以确定剂量,然后在自动悬尾试验中以两种剂量进行研究。所有实验均在盲态下进行。所获得的结果在很大程度上证实了该试验中已报道的活动图谱,并表明将初步观察与自动悬尾试验结合使用能够明确鉴定15种受试化合物的药理活性,对其余3种化合物进行初步鉴定。