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


CONCLUSIONS
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.
Shimamura
Midori
M
Pharmacology Department, Tsukuba Research Laboratories, GlaxoSmithKline, 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan.
Kobayashi
Tomohiro
T
Kuratani
Kazuyoshi
K
Kinoshita
Mine
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D051379:Mice; D012680:Sensitivity and Specificity; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents