De Pablo J M, Parra A, Segovia S, Guillamón A
Departamento de Psicobiología, Universidad Nacional de Educación a Distancia Ciudad Universitaria, Madrid, Spain.
Physiol Behav. 1989 Aug;46(2):229-37. doi: 10.1016/0031-9384(89)90261-8.
The rat forced-swimming test (FST) is widely used for screening substances with a potential antidepressant effect. The rat immobility shown in the FST has been interpreted as "behavioral despair" and has been suggested as an animal model of human depression. In the following series of experiments it is shown that measuring rat mobility by an automatic recording device is more accurate than measuring immobility time by direct observation (Experiment 1 and 5). The automatic recording procedure was tested with imipramine and mianserin showing similar results to those reported in the literature using a direct observation procedure by the researcher (Experiment 2). In Experiment 3 it was demonstrated that: (a) rat mobility decreased with experience, (b) switching water depth on Day 2 of the test increased mobility and (c) anisomycin acts as a false positive. In Experiment 4 the possible state dependent effect of imipramine in the FST was studied. The effect of imipramine on rat behavior in the FST is not state dependent. The imipramine-saline group shows greater mobility than the saline-saline group and does not differentiate from the imipramine-imipramine group. Thus, it was suggested that imipramine could interfere with the acquisition and/or consolidation processes. In Experiment 5, it is shown that a single dose of 25 mg/kg of imipramine, administered before or immediately after training on Day 1, increases rat's mobility on Day 2, thus suggesting that imipramine alters the consolidation process. From these results it is suggested that the behavioral process involved in the FST is "learning to be immobile" instead of "behavioral despair" as previously suggested in the literature.
大鼠强迫游泳试验(FST)被广泛用于筛选具有潜在抗抑郁作用的物质。FST中大鼠的不动状态被解释为“行为绝望”,并被认为是人类抑郁症的动物模型。在以下一系列实验中表明,通过自动记录装置测量大鼠活动能力比直接观察测量不动时间更准确(实验1和5)。用丙咪嗪和米安色林对自动记录程序进行了测试,结果与研究人员使用直接观察程序在文献中报道的结果相似(实验2)。在实验3中证明:(a)大鼠活动能力随经验下降,(b)在测试第2天改变水深可增加活动能力,(c)茴香霉素表现为假阳性。在实验4中研究了丙咪嗪在FST中可能的状态依赖性效应。丙咪嗪对FST中大鼠行为的影响不是状态依赖性的。丙咪嗪-生理盐水组比生理盐水-生理盐水组表现出更大的活动能力,且与丙咪嗪-丙咪嗪组无差异。因此,有人认为丙咪嗪可能会干扰习得和/或巩固过程。在实验5中表明,在第1天训练前或训练后立即给予25mg/kg的丙咪嗪单剂量,可增加大鼠在第2天的活动能力,因此表明丙咪嗪改变了巩固过程。从这些结果可以看出,FST中涉及的行为过程是“学会不动”,而不是如文献中先前提出的“行为绝望”。