Learned immobility explains the behavior of rats in the forced swimming test

Abstract

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.