Tail suspension test

Last updated
tail suspension test (TST) 201407 tail suspension test.png
tail suspension test (TST)
The video is shown at 4x its normal speed : after a period of initial struggle, control mice demonstrate intervals of immobile behavior, reflecting reluctance to maintain active escape-oriented behavior.

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 mouse is subjected to short term inescapable stress then the mouse will become immobile. It is used to measure the effectiveness of antidepressant-like agents but there is significant controversy over its interpretation and usefulness.

Contents

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 2000s where data has shown that animals do show a change in behavior when injected with antidepressants. 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 with depression do not always show the same set of symptoms and often present with co-occurring psychiatric conditions.

A major 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 a condition similar to depression, it is important to keep in mind that depression is, by definition, a human disease. Human and animal brains are considerably different, and care must be taken when interpreting animal behavior and assigning emotional states to various behaviors.

However, there are discrete elements of depression that can be modeled in a lab setting. [3] [4] Stress induced immobilization is a behavior that can be useful in modelling aspects of depression. If a rodent is subjected to the short term inescapable stress of being suspended in the air it will develop an immobile posture. Immobility in the TST can be interpreted as the animal ceasing to put in the effort to try to escape. This is often interpreted as behavioral despair, and could be considered a model of the hopelessness and despair experienced by those with depression. [1]

The main strength of the tail suspension test is its predictive validity– performance on the test can be altered by drugs that improve depressive symptoms in people. Specifically, if antidepressant agents are administered before the test, the animal will struggle for a longer period of time than if not and exhibit more escape behaviors. [1] Thus, it is widely used for assessing the antidepressant effects of new pharmacological compounds.

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 antidepressant-like agents. [5]

Controversy

There are mixed opinions about the TST. A common criticism is that it can be weeks before a noticeable effect is observed in patients who take antidepressants regularly, however the TST only measures one acute antidepressant dose for 5–6 minutes.[ citation needed ]

The TST has predictive reliability for known antidepressant agents. However, when testing drugs of unknown mechanisms, the prediction rate is unclear. While the TST detects NK1 receptor antagonists, which have known antidepressant action, it doesn't detect CRF1 receptor antagonists which also have antidepressant functions.

Some consider the TST to be a test of antidepressant function, rather than a model of depression itself. [6] This is largely because the test measures behavioral response to a short-term stressor, whereas human depression is a long-term condition. [6]

Difference from the forced swim test

TST is more sensitive to antidepressant agents than the FST because the animal will remain immobile longer in the TST than 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. [7] 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

Related Research Articles

<span class="mw-page-title-main">Major depressive disorder</span> Mental disorder involving persistent low mood, low self-esteem, and loss of interest

Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s, the term was adopted by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and has become widely used since.

<span class="mw-page-title-main">Maprotiline</span> Antidepressant

Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary amine. In terms of its chemistry and pharmacology, maprotiline is closely related to such-other secondary-amine TCAs as nortriptyline and protriptyline and has similar effects to them, albeit with more distinct anxiolytic effects. Additionally, whereas protriptyline tends to be somewhat more stimulating and in any case is distinctly more-or-less non-sedating, mild degrees of sedation may be experienced with maprotiline.

<span class="mw-page-title-main">Depression (mood)</span> State of low mood and aversion to activity

Depression is a mental state of low mood and aversion to activity. It affects more than 280 million people of all ages. Depression affects a person's thoughts, behavior, feelings, and sense of well-being. Depressed people often experience loss of motivation or interest in, or reduced pleasure or joy from, experiences that would normally bring them pleasure or joy. Depressed mood is a symptom of some mood disorders such as major depressive disorder and dysthymia; it is a normal temporary reaction to life events, such as the loss of a loved one; and it is also a symptom of some physical diseases and a side effect of some drugs and medical treatments. It may feature sadness, difficulty in thinking and concentration and a significant increase or decrease in appetite and time spent sleeping. People experiencing depression may have feelings of dejection or hopelessness and may experience suicidal thoughts. It can either be short term or long term.

Dysthymia, also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with longer-lasting symptoms. The concept was used by Robert Spitzer as a replacement for the term "depressive personality" in the late 1970s.

Biological psychiatry or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics, epigenetics and physiology to investigate the biological bases of behavior and psychopathology. Biopsychiatry is the branch of medicine which deals with the study of the biological function of the nervous system in mental disorders.

Atypical depression is defined in the DSM-IV as depression that shares many of the typical symptoms of major depressive disorder or dysthymia but is characterized by improved mood in response to positive events. In contrast to those with atypical depression, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also often features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment.

<span class="mw-page-title-main">Suicidal ideation</span> Thoughts, ideas, or ruminations about the possibility of ending ones life

Suicidal ideation, or suicidal thoughts, is the thought process of having ideas, or ruminations about the possibility of completing suicide. It is not a diagnosis but is a symptom of some mental disorders, use of certain psychoactive drugs, and can also occur in response to adverse life events without the presence of a mental disorder.

<span class="mw-page-title-main">Behavioural despair test</span>

The behavioural despair test is a test, centered on a rodent's response to the threat of drowning, whose result has been interpreted as measuring susceptibility to negative mood. It is commonly used to measure the effectiveness of antidepressants, although significant criticisms of its interpretation have been made.

Histone deacetylase inhibitors are chemical compounds that inhibit histone deacetylases. Since deacetylation of histones produces transcriptionally silenced euchromatin, HDIs can render chromatin more transcriptionally active and induce epigenomic changes.

<span class="mw-page-title-main">Depression in childhood and adolescence</span> Pediatric depressive disorders

Major depressive disorder, often simply referred to as depression, is a mental disorder characterized by prolonged unhappiness or irritability. It is accompanied by a constellation of somatic and cognitive signs and symptoms such as fatigue, apathy, sleep problems, loss of appetite, loss of engagement, low self-regard/worthlessness, difficulty concentrating or indecisiveness, or recurrent thoughts of death or suicide.

Animal models of depression are research tools used to investigate depression and action of antidepressants as a simulation to investigate the symptomatology and pathophysiology of depressive illness or used to screen novel antidepressants. These models provide insights into molecular, genetic, and epigenetic factors associated with depression. Criteria for valid animal models include face, construct, and predictive validity. Endophenotypes, such as anhedonia, behavioral despair, changes in appetite, neuroanatomical alterations, neuroendocrine disturbances, alterations in sleep architecture, and anxiety-related behaviors, are evaluated in these models. Antidepressant screening tests are employed to assess the effects of genetic, pharmacological, or environmental manipulations. Stress models, including learned helplessness, chronic mild stress, and social defeat stress, simulate the impact of stressors on depression. Early life stress models, psychostimulant withdrawal models, olfactory bulbectomy, and genetically engineered mice contribute to a comprehensive understanding of depression's etiology and potential therapeutic interventions.

Developed by Calvin S. Hall, the open field test is an experimental test used to assay general locomotor activity levels, anxiety, and willingness to explore in animals in scientific research. However, the extent to which behavior in the open field measures anxiety is controversial. The open field test can be used to assess memory by evaluating the ability of the animal to recognize a stimuli or object. Another animal test that is used to assess memory using that same concept is the novel object recognition test.

The pharmacology of antidepressants is not entirely clear. The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis, which states that depression is due to an imbalance of the monoamine neurotransmitters. It was originally proposed based on the observation that certain hydrazine anti-tuberculosis agents produce antidepressant effects, which was later linked to their inhibitory effects on monoamine oxidase, the enzyme that catalyses the breakdown of the monoamine neurotransmitters. All currently marketed antidepressants have the monoamine hypothesis as their theoretical basis, with the possible exception of agomelatine which acts on a dual melatonergic-serotonergic pathway. Despite the success of the monoamine hypothesis it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, there are a sizeable portion (>40%) of depressed patients that do not adequately respond to monoaminergic antidepressants. Further evidence to the contrary of the monoamine hypothesis are the recent findings that a single intravenous infusion with ketamine, an antagonist of the NMDA receptor — a type of glutamate receptor — produces rapid, robust and sustained antidepressant effects. Monoamine precursor depletion also fails to alter mood. To overcome these flaws with the monoamine hypothesis a number of alternative hypotheses have been proposed, including the glutamate, neurogenic, epigenetic, cortisol hypersecretion and inflammatory hypotheses. Another hypothesis that has been proposed which would explain the delay is the hypothesis that monoamines don't directly influence mood, but influence emotional perception biases.

Bacteriotherapy is the purposeful use of bacteria or their products in treating an illness. Forms of bacteriotherapy include the use of probiotics, microorganisms that provide health benefits when consumed; fecal matter transplants (FMT) /intestinal microbiota transplant (IMT), the transfer of gut microorganisms from the fecal matter of healthy donors to recipient patients to restore microbiota; or synbiotics which combine prebiotics, indigestible ingredients that promote growth of beneficial microorganisms, and probiotics. Through these methods, the gut microbiota, the community of 300-500 microorganism species that live in the digestive tract of animals aiding in digestion, energy storage, immune function and protection against pathogens, can be recolonized with favorable bacteria, which in turn has therapeutic effects.

<span class="mw-page-title-main">Buprenorphine/samidorphan</span> Combination drug formulation

Buprenorphine/samidorphan is a combination formulation of buprenorphine and samidorphan which is under development as an add on to antidepressants in treatment-resistant depression (TRD).

Epigenetics of depression is the study of how epigenetics contribute to depression.

<span class="mw-page-title-main">Marble burying</span> Animal model used in scientific research

Marble burying is an animal model used in scientific research to depict anxiety or obsessive–compulsive disorder (OCD) behavior. It is based on the observation that rats and mice will bury either harmful or harmless objects in their bedding. While widely used there is significant controversy over the interpretation of its results.

<span class="mw-page-title-main">Light-dark box test</span>

The light-dark box test (LDB) is a popular animal model used in pharmacology to assay unconditioned anxiety responses in rodents. The extent to which behavior in the LDB measures anxiety is controversial.

The Vogel conflict test (VCT) is a conflict based experimental method primarily used in pharmacology. It is used to determine anxiolytic properties of drugs. The VCT predicts drugs that can manage generalized anxiety disorders and acute anxiety states.

Immuno-psychiatry, according to Pariante, is a discipline that studies the connection between the brain and the immune system. It differs from psychoneuroimmunology by postulating that behaviors and emotions are governed by peripheral immune mechanisms. Depression, for instance, is seen as malfunctioning of the immune system.

References

  1. 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 (4–5): 571–625. doi:10.1016/j.neubiorev.2005.03.009. PMID   15890404. S2CID   2758433.
  2. American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5 (fifth ed.). Washington D.C.: American Psychiatric Association.
  3. Koob, George; Zimmer, Andreas (2012). "Animal models of psychiatric disorders". Neurobiology of Psychiatric Disorders. Handbook of Clinical Neurology. Vol. 106. pp. 136–166. doi:10.1016/B978-0-444-52002-9.00009-7. ISBN   9780444520029. PMID   22608620.
  4. Cryan, J F; Mombereau, C (13 January 2004). "In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice". Molecular Psychiatry. 9 (4): 326–357. doi:10.1038/sj.mp.4001457. PMID   14743184. S2CID   14937344.
  5. "Tail Suspension Test". Penn State Animal Resource Program. Retrieved 30 March 2016.
  6. 1 2 Hoffman, Kurt Leroy (2016). Modeling Neuropsychiatric Disorders in Laboratory Animals, 2 - What can animal models tell us about depressive disorders?. Woodhead Publishing. pp. 35–36. doi:10.1016/B978-0-08-100099-1.00002-9 . Retrieved 26 February 2022.
  7. Liu, X; Peprah, D; Gershenfield, H.K (2003). "Tail-suspension induced hyperthermia: a new measure of stress reactivity". J Psychiatr Res. 37 (3): 249–259. doi:10.1016/s0022-3956(03)00004-9. PMID   12650744.