The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice

doi:10.1016/j.neubiorev.2005.03.009

Neuroscience & Biobehavioral Reviews

Volume 29, Issues 4–5, 2005, Pages 571-625

https://doi.org/10.1016/j.neubiorev.2005.03.009 Get rights and content

Abstract

Since its introduction almost 20 years ago, the tail suspension test has become one of the most widely used models for assessing antidepressant-like activity in mice. The test is based on the fact that animals subjected to the short-term, inescapable stress of being suspended by their tail, will develop an immobile posture. Various antidepressant medications reverse the immobility and promote the occurrence of escape-related behaviour. This review focuses on the utility this test as part of a research program aimed at understanding the mechanism of action of antidepressants. We discuss the inherent difficulties in modeling depression in rodents. We describe how the tail suspension differs from the closely related forced swim test. Further, we address some key issues associated with using the TST as a model of antidepressant action. We discuss issues regarding whether it satisfies criteria to be a valid model for assessing depression-related behavioural traits. We elaborate on the tests' ease of use, strain differences observed in the test and gender effects in the test. We focus on the utility of the test for genetic analysis. Furthermore, we discuss the concept of whether immobility maybe a behavioural trait relevant to depression. All of the available pharmacological data using the test in genetically modified mice is collated. Special attention is given to selective breeding programs such as the Rouen ‘depressed’ mice which have been bred for high and low immobility in the tail suspension test. We provide an extensive pooling of the pharmacological studies published to date using the test. Finally, we provide novel pharmacological validation of an automated system (Bioseb) for assessing immobility. Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.

Introduction

A man who carries a cat by the tail learns something he can learn in no other way.

attributed to Mark Twain

Since its introduction as a new model for detecting antidepressant activity in 1985, the use of the tail suspension test (TST) demonstrates that Twain's comments can also be translated to mice. The amount of data generated in the subsequent two decades, especially in past 5 years (Fig. 1), have shown that the inescapable stress of suspending a mouse by its tail can give invaluable information about the ability of animals to cope with a stressful situation. Furthermore, and perhaps most importantly for antidepressant drug development, studies with the TST have shown that this coping behaviour can be subsequently altered by pharmacological or genetic manipulations relevant to depression and antidepressant action. This review will focus on the utility of the TST to assess the effects of pharmacological and genetic manipulations relevant to depression and the antidepressant response. Unless otherwise specified the term TST refers to the mouse version of the test.

Section snippets

Modeling depression in rodents

Depression is a heterogeneous, multifaceted disorder with symptoms manifested at the psychological, behavioural and physiological level. This is perhaps why it is so difficult to mimic the disorder in the laboratory (American Psychiatric Association, 1994). Many of the human symptoms of depression, as described in the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM IV) (such as recurring thoughts of death or suicide or having excessive thoughts of guilt) are

The TST more than just a dry-land version of the FST

Like the FST, the TST is based on the observation that rodents (almost always mice although gerbils and rats have been used Varty et al., 2003, Chermat et al., 1986, after initial escape-oriented movements, develop an immobile posture when placed in an inescapable stressful situation. In the case of the TST the stressful situation involves the haemodynamic stress of being hung in an uncontrollable fashion by their tail whereas in the FST mice are placed in a cylinder filled with water (Thierry

Does the TST meet validity criteria?

Many authors have proposed validity criteria for animal models of depression, with those proposed by McKinney and Bunney (1969) over 30 years ago still the most cited. These authors propose that the validity of an animal model can be determined by the extent that: (i) it is ‘reasonably analogous’ to the human disorder in its manifestations or symptomatology; (ii) there is a behavioural change that can be objectively monitored; (iii) the behavioural changes observed should be reversed by the

The Rouen ‘Depressed’ (a.k.a. H/Rouen) mice

To shed light on the potential genetic contribution on ‘depressive-like’ behaviour, several attempts have been undertaken to selectively breed animals based on their individual responsiveness in animal models of depression. To date, these breeding efforts have, however, largely focused on rat models. Rats have been selectively bred for susceptible to learned helplessness Edwards et al., 2000, Kohen et al., 2003, Vollmayr and Henn, 2001 and for high and low level of immobility in the FST (Scott

Pharmacological validation of the TST

Within the literature there are excellent reviews on the effects of pharmacological or other manipulations on the behaviour of rodents in various behavioural paradigms used in psychopharmacological research; these include tests such as the forced swim test Borsini and Meli, 1988, Borsini, 1995, prepulse inhibition of the startle reflex Geyer et al., 2001, Geyer et al., 2002; latent-inhibition (Moser et al., 2000); open field test (Prut and Belzung, 2003); stress-induced hyperthermia (Olivier et

Validation of an automated TST (Bioseb)

As is obvious from the previous sections and Table 2, numerous studies have shown that antidepressant-induced behavioural changes in the TST can be influenced by many factors (e.g., strain etc.). We have recently introduced the TST into our depression test battery. However, there were a number of factors that needed to be validated, as we used a newly launched automated system (Bioseb, France). The use of automation is advantageous for our drug screening process, as it results in unbiased, fast

Conclusions

The TST has great utility as a model to assess antidepressant-related behaviour, however its use is best exploited when used in battery style fashion with other depression models such as FST, learned helplessness, anhedonia models and olfactory bulbectomy. Further, it is clear that to date the TST is not as well characterized as the FST in terms of the breadth of treatments tested or the number of depression-inducing manipulations tested; such future analysis is certain to increase the

Acknowledgements

JFC is supported by National Institutes of Mental Health/National Institute on Drug Abuse grant U01 MH69062. CM is a doctoral student affiliated with the Laboratoire de Neuroscience Cognitives, CNRS UMR 5106, Université de Bordeaux 1, Avenue des Facultés, Talence cedex 33405, France. The authors would like to thank Dr Conrad Gentsch and Dr Athina Markou for their critical reading of the manuscript, Mr Martin Schaub for excellent technical expertise and Mr Jacques Desevre (Bioseb, France) for

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ReviewThe tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice

Abstract

Introduction

Section snippets

Modeling depression in rodents

The TST more than just a dry-land version of the FST

Does the TST meet validity criteria?

The Rouen ‘Depressed’ (a.k.a. H/Rouen) mice

Pharmacological validation of the TST

Validation of an automated TST (Bioseb)

Conclusions

Acknowledgements

Sleep Med Rev

Behav Biol

Pharmacol Biochem Behav

Physiol Behav

Eur J Pharmacol

Neurosci Biobehav Rev

Neurosci Biobehav Rev

Eur J Pharmacol

Life Sci

Biol Psychiatry

Pharmacol Biochem Behav

Eur J Pharmacol

Neuropharmacology

Pharmacol Biochem Behav

Trends Pharmacol Sci

Eur J Pharmacol

Biol Psychiatry

Behav Brain Res

Pharmacol Biochem Behav

Prog Neuropsychopharmacol Biol Psychiatry

Am J Hypertens

Pharmacol Res

Eur J Pharmacol

Pharmacol Biochem Behav

Jpn J Pharmacol

Eur J Pharmacol

Clin Neurosci Res

Acta Psychol (Amst)

Pharmacol Biochem Behav

Brain Res Bull

Eur J Pharmacol

Prog Neuropsychopharmacol Biol Psychiatry

Neuropsychopharmacology

Curr Opin Genet Dev

Brain Res

Life Sci

Pharmacol Biochem Behav

Behav Brain Res

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Eur J Pharmacol

Neurosci Lett

Neuropharmacology

Pharmacol Biochem Behav

Biol Psychiatry

Pharmacol Biochem Behav

Diagnostic and statistical manual of mental disorders

Effect of castration and testosterone in experimental models of depression in mice

Behav Neurosci

Diminished anxiety- and depression-related behaviors in mice with selective deletion of the Tac1 gene

J Neurosci

Sex differences in mesolimbic dopamine responses to ethanol and relationship to ethanol intake in rats

Recent Dev Alcohol

Review
The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice