Use of latency to immobility improves detection of antidepressant-like activity in the behavioral despair test in the mouse

The behavioral despair test (BDT), also called the forced swim test, is an economic, reliable and sensitive test for the detection of potential antidepressant-like activity of new test substances. The vast majority of clinically active antidepressants are active in the BDT, although substances specifically acting on serotonin transmission are generally reported to be less easily detected. Substances active in the BDT decrease the duration of immobility at doses considered as relatively high. In contrast, some psychostimulants are considered as potential false positives since they are also active in the BDT although they are not recognized as clinically active antidepressants. In the present study we have evaluated the usefulness of latency to the first immobility period as an additional parameter in the BDT to further evaluate the effects of antidepressants and psychostimulants administered intraperitoneally in the mouse. The results show that this measure increases the sensitivity of the test for detecting the effects of tricyclic antidepressants (imipramine, desipramine) and selective serotonin/norepinephrine reuptake inhibitors (duloxetine and venlafaxine) but not of serotonin reuptake inhibitors (fluoxetine and escitalopram). In contrast with previous reports, psychostimulants (amphetamine and modafinil) did not affect the duration or the latency to immobility in the BDT. The mouse strain used in the BDT seems to be an important parameter to discriminate between antidepressants and psychostimulants. These results suggest that the measure of the latency to the first immobility improves the predictive validity of the BDT.