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The tail suspension test (TST) is an experimental method used to measure stress in rodents in scientific research. It is based on the observation that if a rat is subjected to short term inescapable stress then the rat will become immobile. It is used to measure the effectiveness of anti-depressant like agents but there is significant controversy over its interpretation.

History
The TST was introduced in 1985 due to the popularity of a similar test called the forced swim test (FST.) Researcher wanted a better way to screen anti-depression like agents. However this test only recently became popular in the 2000’s where data has shown that animals do show a change in behavior when injected with anti-depressants. This test is far more reliable when done in conjuncture with other depression models such as FST, learned helplessness, anhedonia models and olfactory bulbectomy.

Concept
Depression is a complex multi-faceted disorder with many symptoms rooted in the psychological, behavioral, and genetic level. Since it is so complex it is hard to model in a lab setting due to the many variables.

Another difficulty in modeling depression is that psychiatrists who clinically diagnose depression follow the Diagnostic and Statistical Manual (DSM IV) of the American Psychiatric Association, which involves self-reporting from patients on how they feel. Since animals cannot explain to us how they feel, animals cannot be diagnosed as clinically depressed.

While there are theories that say animals can be depressed it is also important to keep in mind that human brains are also much more complex then rat brains which means that the way humans process emotion can be very different from how animals such as rats and mice process emotion which makes it even more difficult to determine if animals can experience depression.

There are however some symptoms that be modeled in a lab setting one of which is stress. One of these symptoms is stress which is very common in depression. If a rodent is subjected to the short term inescapable stress of being suspended in the air it will develop an immobile posture. If anti-depressant agents are injected before the test is done however, the animal will struggle for a longer period of time then a rat that has not been injected.

Procedure
The animal is hung from a tube by its tail for five minutes approximately 10 cm away from the ground. The time it takes until it finally remains immobile is measured. Each animal is tested only once and out of view from the other animals. There should be two sets of rats, one group which is the control and the other group which has been injected with the anti-depressants like agent.

Immobility is defined as that the animal doesn’t want to put in the effort to try to escape. This is representing a common symptom in depression that people don’t put in a lot of effort into activities due to all the stress they feel.

Controversy
There are mixed opinions about TST. One is that when patients usually take anti-depressants clinically it can be weeks before a noticeable effect is observed. TST only measures the anti-depressants action for five minutes.

The test also has a genetic component to it. Some strains of mice instead of struggling will attempt to climb their own tail in order to escape. Since this doesn’t measure immobility due to stress they cannot be used. Other strains of mice also respond differently to anti-depressants meaning the test can only be done with certain strains. Since different responses can be observed it can affect how reproducible the experiment is.

Behavior of animal being tested can vary depending on environmental factors. Even though measures have been taken to standardize the test, differences in labs provide different environmental factors which again raises into question how reproducible the experiment really is.

When testing known anti-depressant agents, TST had a good prediction rate for them. However when testing drugs whose mechanism of action is unknown, the prediction rate is unclear. TST detects NK1 receptor antagonists but doesn’t detect CRF1 receptor antagonists.

Difference from the forced swim test
The TST and FST while similar are different. The TST arguably actually better than the FST. The TST is more sensitive to anti-depressant agents then the FST because the animal will actually remain immobile longer in the TST then the FST. Another is that the immobility in the FST could be due to the shock experienced by the animal when it is dropped into the water which also risks hypothermia. Also the mechanisms through which the TST and FST produce stress while overlapping are actually different.