Tail suspension test
The tail suspension test (TST) is an experimental method used in scientific research to measure stress in rodents. 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 and usefulness.
History
The TST was introduced in 1985 due to the popularity of a similar test called the forced swim test (FST). 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. TST is more reliable when done in conjunction with other depression models such as FST, learned helplessness, anhedonia models and olfactory bulbectomy.[1]
Modeling Depression
Depression is a complex multi-faceted disorder with symptoms that can have multiple causes such as psychological, behavioral, and genetics. Since there are so many variables it is hard to model in a lab setting.Patients suffering from depression do not always show the same set of symptoms.
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.[2]
While there are theories that animals can experience depression it is important to keep in mind that human brains are much more complex then rat brains. Since the brains are different the way emotion is processed could also be different. These uncertainties makes it difficult to determine if animals can experience depression.[3]
However there are symptoms that be modeled in a lab setting one of which is stress induced immobilization. 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, the animal will struggle for a longer period of time then an animal that has not.[1]
Immobility in the TST is defined as when the animal doesn’t want to put in the effort to try to escape. This represents a common symptom in depression where people who suffer from depression don’t put a lot of effort into activities due to stress.[1]
Procedure
The animal is hung from a tube by its tail for five minutes approximately 10 cm away from the ground. During this time the animal will try to escape and reach for the ground. The time it takes until it remains immobile is measured. Each animal is tested only once and out of view from the other animals. Within the study there should be two sets of rats, one group which is the control which has been injected with saline and the group being tested which has been injected with the anti-depressant like agents.[4]
Controversy
There are mixed opinions about TST. One is that it can be weeks before a noticeable effect is observed in patients who take anti-depressants regularly. TST measures one acute anti-depressants dose 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 these mice cannot be used. Other strains of mice will respond differently to anti-depressants. Since different responses can be observed it affects how reproducible the experiment is. This component raises into question that if the results aren't even the same within a species then how can they be the same in humans.[5]
The behavior of rodents varies depending on environmental factors. Even though measures have been taken to standardize the test, differences between labs produce different factors which effects the reproducibility of the experiment.[5]
TST has a good prediction rate for known anti-depressant agents. However when testing drugs whose mechanism of action is unknown, the prediction rate is unclear. While TST detects NK1 receptor antagonists which have known anti-depressant action it doesn't detect CRF1 receptor antagonists which also have antidepressant functions.
Difference from the forced swim test
TST is more sensitive to anti-depressant agents then the FST because the animal will remain immobile longer in the TST then the FST.[1] The FST is not as reliable as the TST because the immobility in the animal could be due to the shock of being dropped in water. This also risks hypothermia.[6] While the mechanisms through which the TST and FST produce stress are unknown it is clear that while overlapping the tests produce immobility through stress differently.
See also
References
- 1 2 3 4 Cryan, John F.; Mombereau, Cedric; Vassout, Annick (2005). "The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice". Neuroscience and Biobehavioral Reviews 29 (29): 571–625.
- ↑ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (fifth ed.). Washington D.C: American Psychiatric Association.
- ↑ Cryan, JF; Mombereau, C (2004). "In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice". Molecular Psychiatry (9): 326–357.
- ↑ "Tail Suspension Test". Penn State Animal Resource Program. Retrieved 30 March 2016.
- 1 2 Lucki, I; Dalvi, A; Mayorga, A.J (2001). "Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice.". Psychopharmacology 155: 315–322.
- ↑ Liu, X; Peprah, D; Gershenfield, H.K (2003). "Tail-suspension induced hyperthermia: a new measure of stress reactivity.". J Psychiatr Res 37: 249–259.