Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

Using the rat forced swim test to assess antidepressant-like activity in rodents

Abstract

The forced swim test (FST) is one of the most commonly used animal models for assessing antidepressant-like behavior. This protocol details using the FST in rats, which takes place over 48 h and is followed by the video analysis of the behavior. The swim test involves the scoring of active (swimming and climbing) or passive (immobility) behavior when rodents are forced to swim in a cylinder from which there is no escape. There are two versions that are used, namely the traditional and modified FSTs, which differ in their experimental setup. For both versions, a pretest of 15 min (although a number of laboratories have used a 10-min pretest with success) is included, as this accentuates the different behaviors in the 5-min swim test following drug treatment. Reduction in passive behavior is interpreted as an antidepressant-like effect of the manipulation, provided it does not increase general locomotor activity, which could provide a false positive result in the FST.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kessler, R.C. et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). J. Am. Med. Assoc. 289, 3095–3105 (2003).

    Article  Google Scholar 

  2. Murray, C.J. & Lopez, A.D. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 349, 1498–1504 (1997).

    Article  CAS  Google Scholar 

  3. Licinio, J. & Wong, M.L. Depression, antidepressants and suicidality: a critical appraisal. Nat. Rev. Drug Discov. 4, 165–171 (2005).

    Article  CAS  Google Scholar 

  4. Matthews, K., Christmas, D., Swan, J. & Sorrell, E. Animal models of depression: navigating through the clinical fog. Neurosci. Biobehav. Rev. 29, 503–513 (2005).

    Article  Google Scholar 

  5. Porsolt, R.D., Le Pichon, M. & Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature 266, 730–732 (1977).

    Article  CAS  Google Scholar 

  6. Porsolt, R.D., Bertin, A. & Jalfre, M. 'Behavioural despair' in rats and mice: strain differences and the effects of imipramine. Eur. J. Pharmacol. 51, 291–294 (1978).

    Article  CAS  Google Scholar 

  7. Porsolt, R.D., Anton, G., Blavet, N. & Jalfre, M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 47, 379–391 (1978).

    Article  CAS  Google Scholar 

  8. Cryan, J.F. & Holmes, A. The ascent of mouse: advances in modelling human depression and anxiety. Nat. Rev. Drug Discov. 4, 775–790 (2005).

    Article  CAS  Google Scholar 

  9. Petit-Demouliere, B., Chenu, F. & Bourin, M. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl.) 177, 245–255 (2005).

    Article  CAS  Google Scholar 

  10. Porsolt, R.D., Bertin, A. & Jalfre, M. Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther. 229, 327–336 (1977).

    CAS  PubMed  Google Scholar 

  11. Rupniak, N.M. et al. Comparison of the phenotype of NK1R−/− mice with pharmacological blockade of the substance P (NK1) receptor in assays for antidepressant and anxiolytic drugs. Behav. Pharmacol. 12, 497–508 (2001).

    Article  CAS  Google Scholar 

  12. Einat, H., Kronfeld-Schor, N. & Eilam, D. Sand rats see the light: short photoperiod induces a depression-like response in a diurnal rodent. Behav. Brain. Res. 173, 153–157 (2006).

    Article  Google Scholar 

  13. Lucki, I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav. Pharmacol. 8, 523–532 (1997).

    Article  CAS  Google Scholar 

  14. Cryan, J.F., Markou, A. & Lucki, I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol. Sci. 23, 238–245 (2002).

    Article  CAS  Google Scholar 

  15. Cryan, J.F. & Mombereau, C. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol. Psychiatry 9, 326–357 (2004).

    Article  CAS  Google Scholar 

  16. Slattery, D.A., Desrayaud, S. & Cryan, J.F. GABAB receptor antagonist-mediated antidepressant-like behavior is serotonin-dependent. J. Pharmacol. Exp. Ther. 312, 290–296 (2005).

    Article  CAS  Google Scholar 

  17. Cryan, J.F., Valentino, R.J. & Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci. Biobehav. Rev. 29, 547–569 (2005).

    Article  CAS  Google Scholar 

  18. Borsini, F. & Meli, A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl.) 94, 147–160 (1988).

    Article  CAS  Google Scholar 

  19. Slattery, D.A., Neumann, I.D. & Cryan, J.F. Transient inactivation of the infralimbic cortex induces antidepressant-like effects in the rat. J. Psychopharmacol. (Oxford, England) 25, 1295–1303 (2011).

    Article  Google Scholar 

  20. Slattery, D.A. & Cryan, J.F. Animal models of depression – where are we going? in Depression from Psychopathology to Pharmacotherapy (eds. J.F. Cryan & B.E. Leonard) (S. Karger, Basel, 2011).

  21. Katz, M.M., Bowden, C.L. & Frazer, A. Rethinking depression and the actions of antidepressants: uncovering the links between the neural and behavioral elements. J. Affect. Disord. 120, 16–23.

  22. Cryan, J.F., Page, M.E. & Lucki, I. Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology (Berl.) 182, 335–344 (2005).

    Article  CAS  Google Scholar 

  23. Detke, M.J., Johnson, J. & Lucki, I. Acute and chronic antidepressant drug treatment in the rat forced swimming test model of depression. Exp. Clin. Psychopharmacol. 5, 107–112 (1997).

    Article  CAS  Google Scholar 

  24. Cryan, J.F. & Slattery, D.A. Animal models of mood disorders: recent developments. Curr. Opin. Psychiatry 20, 1–7 (2007).

    Article  Google Scholar 

  25. Gould, T.D. & Gottesman, I.I. Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav. 5, 113–119 (2006).

    Article  CAS  Google Scholar 

  26. Hasler, G., Drevets, W.C., Gould, T.D., Gottesman, I.I. & Manji, H.K. Toward constructing an endophenotype strategy for bipolar disorders. Biol. Psychiatry 60, 93–105 (2006).

    Article  Google Scholar 

  27. Ravindran, A.V., Matheson, K., Griffiths, J., Merali, Z. & Anisman, H. Stress, coping, uplifts, and quality of life in subtypes of depression: a conceptual frame and emerging data. J. Affect. Disord. 71, 121–130 (2002).

    Article  Google Scholar 

  28. Morley-Fletcher, S. et al. Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats. Neuropharmacology 47, 841–847 (2004).

    Article  CAS  Google Scholar 

  29. Rygula, R. et al. Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav. Brain Res. 162, 127–134 (2005).

    Article  Google Scholar 

  30. Rygula, R. et al. Citalopram counteracts depressive-like symptoms evoked by chronic social stress in rats. Behav. Pharmacol. 17, 19–29 (2006).

    Article  CAS  Google Scholar 

  31. Hill, M.N., Brotto, L.A., Lee, T.T. & Gorzalka, B.B. Corticosterone attenuates the antidepressant-like effects elicited by melatonin in the forced swim test in both male and female rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 905–911 (2003).

    Article  CAS  Google Scholar 

  32. Brotto, L.A., Gorzalka, B.B. & Barr, A.M. Paradoxical effects of chronic corticosterone on forced swim behaviours in aged male and female rats. Eur. J. Pharmacol. 424, 203–209 (2001).

    Article  CAS  Google Scholar 

  33. Cryan, J.F., Hoyer, D. & Markou, A. Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol. Psychiatry 54, 49–58 (2003).

    Article  CAS  Google Scholar 

  34. Detke, M.J. & Lucki, I. Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth. Behav. Brain Res. 73, 43–46 (1996).

    Article  CAS  Google Scholar 

  35. Jacobson, L.H. & Cryan, J.F. Feeling strained? Influence of genetic background on depression-related behavior in mice: a review. Behav. Genet. 37, 171–213 (2007).

    Article  CAS  Google Scholar 

  36. Lucki, I., Dalvi, A. & Mayorga, A.J. Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl.) 155, 315–322 (2001).

    Article  CAS  Google Scholar 

  37. Lopez-Rubalcava, C. & Lucki, I. Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology 22, 191–199 (2000).

    Article  CAS  Google Scholar 

  38. Overstreet, D.H., Rezvani, A.H. & Parsian, A. Behavioural features of alcohol-preferring rats: focus on inbred strains. Alcohol Alcohol. 34, 378–385 (1999).

    Article  CAS  Google Scholar 

  39. Friedman, E., Berman, M. & Overstreet, D. Swim test immobility in a genetic rat model of depression is modified by maternal environment: a cross-foster study. Dev. Psychobiol. 48, 169–177 (2006).

    Article  Google Scholar 

  40. Scott, P.A., Cierpial, M.A., Kilts, C.D. & Weiss, J.M. Susceptibility and resistance of rats to stress-induced decreases in swim-test activity: a selective breeding study. Brain Res. 725, 217–230 (1996).

    Article  CAS  Google Scholar 

  41. West, C.H. & Weiss, J.M. A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test. Psychopharmacology (Berl.) 182, 9–23 (2005).

    Article  CAS  Google Scholar 

  42. Cryan, J.F., Page, M.E. & Lucki, I. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test. Eur. J. Pharmacol. 436, 197–205 (2002).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

D.A.S. and J.F.C. contributed equally to the manuscript.

Corresponding author

Correspondence to David A Slattery.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Video 1

Example of immobility behavior (MOV 979 kb)

Supplementary Video 2

Example of swimming behavior (MOV 2839 kb)

Supplementary Video 3

Example of climbing behavior (MOV 3263 kb)

Supplementary Data 1

Example of results and analysis of a dataset (XLSX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slattery, D., Cryan, J. Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc 7, 1009–1014 (2012). https://doi.org/10.1038/nprot.2012.044

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2012.044

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research