Optimized analysis of the forced swim test using an automated experimental system: Detailed time course study in mice

Introduction: In most publications on the forced swim test studies, duration of immobility is measured during the last 4 min of the 6-min testing period as a marker for depression. However, it is not clear if 4-min span best captures antidepressant-like drug effects. In the present study, six typical antidepressants in clinical use were evaluated over time. Imipramine (60 mg/kg, PO), desipramine (60 mg/kg, PO), reboxetine (20 mg/kg, IP), bupropion (60 mg/kg, PO), fluoxetine (20 mg/kg, PO) and fluvoxamine (60 mg/kg, PO) were characterized over 1-min intervals for the 6-min testing period in order to identify more sensitive periods than the last 4-min span to detect drug effects, using the automated experimental system. Methods: One day before the testing, wire rings were attached to the hind paws of male CD-1 mice. On the test day, after attaching a small magnet to the wire rings, each animal was placed for 6 min in a glass cylinder filled with water, which is surrounded by a coil. The duration of immobility was measured by the previously validated automated detection system, MicroAct™, i.e. electrical signals generated by limb movements served as the marker for swimming behavior. Results: In the 1-min interval examination, it was only in 2–3-min and 3–4-min spans that all of the six antidepressants reduced the duration of immobility with statistical significance. In the 2–4-min analysis, all of the six antidepressants demonstrated statistically significant reduction in the duration of immobility, while in the 2–6-min analysis, the reduction by fluvoxamine was not statistically significant. Discussion: The detailed time course analysis of the FST in mice using the automated system revealed that the duration of immobility between 2 and 4 min is the optimum period to capture the antidepressant-like effect of test compounds.