A new automated and high-throughput system for analysis of the forced swim test in mice based on magnetic field changes.
BACKGROUND
MicroAct (Neuroscience, Tokyo, Japan) was originally developed as a new system for an automated analysis of scratching behaviors in mice. This system is based on the detection of electric current in the coils according to the movement of the magnets implanted in the hind paws. We applied and improved this system to establish an automated analysis system of forced swimming behaviors in mice, which is used as an animal model of depression.


METHODS
One day before the test, male CD-1 mice were attached with a wire ring to their hind paws under inhalation anesthesia. After attaching a small magnet to both of the wire rings, each animal was placed for 6 min in a glass cylinder filled with water, which is surrounded by a coil. The swimming behaviors of the mouse were analyzed for the measurement of duration of immobility, a major marker of depression in rodents, by the detection system (MicroAct). The duration of immobility was also determined by manual measurement using the swimming behavior-recorded videotapes produced at the same time as the automated analysis.


RESULTS
The difference of the duration of immobility between naïve mice and mice with the rings was not significant. The dose-response effect of imipramine (tricyclic antidepressant, 0, 7.5, 15, 30 and 60 mg/kg, p.o.) on the duration of immobility in the last 4-min of the 6-min testing period determined by MicroAct was similar to that assessed by the manual measurement. These data from the two different methods were significantly correlated (r=0.8805). Moreover, throughput of the automated analysis was 15 times more efficient than that of the manual analysis.


CONCLUSIONS
These results suggest that the automated analysis system of forced swimming of mice using MicroAct can be used as a high-throughput method to examine antidepressive activity of a compound with objectivity and reliability.
Shimamura
Midori
M
Pharmacology Department, Tsukuba Research Laboratories, GlaxoSmithKline, 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan.
Kuratani
Kazuyoshi
K
Kinoshita
Mine
M
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001331:Automation; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004574:Electromagnetic Fields; D004867:Equipment Design; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013550:Swimming; D014741:Video Recording
D000929:Antidepressive Agents, Tricyclic; D007099:Imipramine