JoVE Journal > Behavior
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Abstract
Introduction
Protocol
Results
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Behavior

Forced Swim-Test als ein Modell der Depressive ähnliche Verhalten

Published: March 02, 2015
doi:
10.3791/52587
, , ,
1School of Psychological Sciences,Tel-Aviv University, 2School of Behavioral Sciences,Academic College of Tel Aviv-Yaffo, 3Department of Education and Psychology,The Open University of Israel, 4School of Health and Life Sciences,Hadassah Academic College

Summary

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

Abstract

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

Introduction

Depression ist eine lebensbedrohliche psychiatrische Störung und eine große öffentliche Gesundheit betreffen weltweit mit einer Häufigkeit von 5% und einer Lebenszeitprävalenz von 15-20%. Darüber hinaus wird geschätzt, dass bis zum Jahr 2020 Depressionen in den ersten drei Beiträge zur Krankheitslast 1,2 sein. Depression ist mit Behinderung verbunden sind, verringert die Lebensqualität, erhöhte Gesundheitskosten und wird für viele Krankheiten, einschließlich Herz-Kreislauf, Stoffwechsel und neuropsychiatrischen Störungen 3,4 .Current pharmazeutisch-therapeutische Behandlungen Wirksamkeit begrenzt und werden im Zusammenhang mit als Hauptrisikofaktor viele schädliche Nebenwirkungen 5,6. Daher bleibt ein besseres Verständnis der Pathophysiologie dieser Erkrankung neben der Entwicklung von innovativen und verbesserten Behandlung entscheidend. Daher sind Tiermodelle wesentlichen zum Vorschieben Forschung auf diesem Gebiet.

Es gibt viele Modelle für die Untersuchung dieser Erkrankung (verwendet <em> zB Saccharose Präferenztest, Schwanz Suspensionstest) mit dem Zwangsschwimmtest (FST, der auch als Porsolt-Test nach der Entwickler dieser Modell 7,8 bekannt), einer der am häufigsten verwendeten Tests 7,9-12.

Während der FST ein Tier in einem Behälter mit Wasser aus dem sie nicht entweichen können gefüllt war. Das Tier wird zuerst versuchen zu fliehen, aber schließlich wird Immobilität (dh schwimmend mit dem Fehlen einer Bewegung mit Ausnahme derjenigen, für die Führung der Nase über Wasser erforderlich) aufweisen. Die FST ist ein sehr beliebtes Modell in Tierversuchen für eine Reihe von Gründen. Zunächst geht es um die Exposition der Tiere auf Stress, von dem gezeigt wurde, eine Rolle in der Tendenz für die Hauptdepression 12-14 haben. Außerdem Depression wird oft als mangelnde Fähigkeit, mit Stress 15-17 behandeln angesehen. Zweitens pharmakologische Behandlung mit Antidepressiva vor der Prüfung hat sich gezeigt, Unbeweglichkeit in der FST <reduzierensup> 18-23. Daher wird häufig als Screening-Test an neuen Verbindungen mit potentiellen antidepressive Eigenschaften 15-17,24 verwendet. Zusätzlich kann die FST ist gezeigt worden, einige der Faktoren, beeinflußt werden oder durch Drücken in Menschen verändert, wie beispielsweise Veränderungen bei der Nahrungsaufnahme, Schlafanomalien und gemeinsam Drogenentzug-induzierte Anhedonie 15-17,24. Dies ist auch der Grund, warum dieser Test wird manchmal verwendet, um depressive Verhalten in mutierten Mäusen, mit Zunahme oder Abnahme der basalen Unbeweglichkeit zu bewerten (im Vergleich zur "Wildtyp" Mäuse) 25,26.

Protocol

HINWEIS: Alle Versuchsprotokolle wurden durch das Internationale Komitee für Animal Care und Verwenden in Israel zugelassen. Alle Anstrengungen wurden unternommen, um die Zahl der verwendeten Tiere und ihr Leiden zu minimieren. 1. Vorbereitung für die Zwangsschwimmtest Verwenden Sie zwei benachbarte Zimmer. Verwenden Sie ein Zimmer als "Warteraum" für den Verhaltenstests halten die Tiere vor, und die andere für die Durchführung des Verfahrens. Bereiten tra…

Representative Results

Die folgenden Ergebnisse werden auf unveröffentlichte Daten aus unserem Labor beruht. In diesem Experiment wurden erwachsene weibliche ICR-Mäuse nach 3 Wochen der Behandlung mit dem selektiven Serotonin-Wiederaufnahmehemmer (SSRI) Escitalopram oder neuartige pflanzliche antidepressiven und Anti-Angst-Behandlung (NHT) getestet (für zusätzliche Informationen über die pflanzliche Behandlung, siehe 12 , 27,28). Einweg-ANOVA ergab, dass die Behandlung reduziert depressive Verhalten in der FST [F (2,58) = 4,88…

Discussion

Die FST wird zur Behandlung depressiver artiges Verhalten zu überwachen und auf der Annahme, dass Immobilität reflektiert ein Maß behavioral despair 3 bezogen. Die wesentlichen Vorteile dieses Verfahrens liegen in der relativ einfachen Betrieb und schnelle Ergebnisse. Darüber hinaus ist seine Empfindlichkeit gegenüber einem breiten Spektrum von Antidepressiva, die ihn zu einem geeigneten Screening-Test ist eine der wichtigsten Eigenschaften, die zu ihrer hohen prognostische Validität 29. Wich…

Disclosures

The authors have nothing to disclose.

Acknowledgements

This research was supported by the Israel Science Foundation (grant No. 738/11), by the National Institute for Psychobiology in Israel (NIPI-7-2011-12), and by the Open University Foundation

Materials

Name of Material/ Equipment Company Catalog Number Comments/Description
Computer Dell intel(r) core(tm) i3-2120 cpu @ 3.30ghz, 4GB ram
Camera VIDO AU-CB422 B/W CCD CAMERA 
http://www.vido-europe.com/products_detail.asp?id=33&pcategory=2
Coding software Biobserve FST Analysis
http://www.biobserve.com/products/fst/index.html
Heating lamp Ikea AA-19025-3 ESPRESSIVIO 400.504.46 - 20W G4 Bulb 
http://www.ikea.com/ms/en_US/customer_service/assembly/E/E00050467.pdf
Heating pillow Sachs EF-188B 38*38cm Heating pillow
http://www.sachs.co.il/eng/lego_tree.php?instance_id=21&actions=show&id=
604
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References

  1. Levinson, D. F. The genetics of depression: a review. Biological psychiatry. 60, 84-92 (2006).
  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).
  3. Cryan, J. F., Holmes, A. The ascent of mouse: advances in modelling human depression and anxiety. Nature reviews. Drug discovery. 4, 775-790 (2005).
  4. Thase, M. E. Managing depressive and anxiety disorders with escitalopram. Expert opinion on pharmacotherapy. 7, 429-440 (2006).
  5. Lam, R. W., Kennedy, S. H. Evidence-based strategies for achieving and sustaining full remission in depression: focus on metaanalyses. Canadian journal of psychiatry. Revue canadienne de psychiatrie. 49, 17S-26S (2004).
  6. Dording, C. M., et al. The pharmacologic management of SSRI-induced side effects: a survey of psychiatrists. Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists. 14, 143-147 (2002).
  7. Porsolt, R. D., Le Pichon, M., Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 266, 730-732 (1977).
  8. Porsolt, R. D., Bertin, A., Jalfre, M. Behavioral despair in mice: a primary screening test for antidepressants. Archives internationales de pharmacodynamie et de therapie. 229, 327-336 (1977).
  9. Cryan, J. F., Markou, A., Lucki, I. Assessing antidepressant activity in rodents: Recent developments and future needs. Trends in Pharmacological Sciences. 23, 238-245 (2002).
  10. Cryan, J. F., et al. Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors. Proceedings of the National Academy of Sciences of the United States of America. 101, 8186-8191 (2004).
  11. Porsolt, R. D., Anton, G., Blavet, N., Jalfre, M. Behavioural despair in rats: A new model sensitive to antidepressant treatments. European Journal of Pharmacology. 47, 379-391 (1978).
  12. Doron, R., et al. A novel herbal treatment reduces depressive-like behaviors and increases BDNF levels in the brain of stressed mice. Life sciences. 94, 151-157 (2014).
  13. Caspi, A., et al. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science. 301, 386-389 (2003).
  14. Kaufman, J., et al. Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological psychiatry. 59, 673-680 (2006).
  15. Anisman, H., Zacharko, R. M. Multiple neurochemical and behavioral consequences of stressors: Implications for depression. Pharmacology and Therapeutics. 46, 119-136 (1990).
  16. Kessler, R. C. The effects of stressful life events on depression. Annual Review of Psychology. 48, 191-214 (1997).
  17. Sullivan, P. F., Neale, M. C., Kendler, K. S. Genetic epidemiology of major depression: Review and meta-analysis. American Journal of Psychiatry. 157, 1552-1562 (2000).
  18. Cryan, J. F., Valentino, R. J., Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and biobehavioral reviews. 29, 547-569 (2005).
  19. Detke, M. J., Lucki, I. Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: The effects of water depth. Behavioural Brain Research. 73, 43-46 (1996).
  20. Hemby, S. E., et al. Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters. Journal of Pharmacology and Experimental Therapeutics. 282, 727-733 (1997).
  21. Bouvard, M., Stinus, L. In the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments may produce greater effects than selective drugs. Behavioural Brain Research. 136, 521-532 (2002).
  22. Page, M. E., Detke, M. J., Dalvi, A., Kirby, L. G., Lucki, I. Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology. 147, 162-167 (1999).
  23. Rubalcava, C., Lucki, I. Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology. 22, 191-199 (2000).
  24. Cryan, J. F., Mombereau, C., Vassout, A. The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice. Neuroscience and biobehavioral reviews. 29, 571-625 (2005).
  25. Cryan, J. F., Mombereau, C. In search of a depressed mouse: Utility of models for studying depression-related behavior in genetically modified mice. Molecular Psychiatry. 9, 326-357 (2004).
  26. Sang, K. P., et al. Par-4 links dopamine signaling and depression. Cell. 122, 275-287 (2005).
  27. Doron, R., et al. Anxiolytic effects of a novel herbal treatment in mice models of anxiety. Life sciences. 90, 995-1000 (2012).
  28. Doron, R., et al. Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications. PloS one. 9, e91455 (2014).
  29. Borsini, F., Meli, A. Is the forced swimming test a suitable model for revealing antidepressant activity. Psychopharmacology. 94, 147-160 (1988).
  30. Reinhold, J. A., Mandos, L. A., Rickels, K., Lohoff, F. W. Pharmacological treatment of generalized anxiety disorder. Expert opinion on pharmacotherapy. 12, 2457-2467 (2011).
  31. Estrada-Camarena, E., Fernandez-Guasti, A., Lopez-Rubalcava, C. Interaction between estrogens and antidepressants in the forced swimming test in rats. Psychopharmacology. 173, 139-145 (2004).
  32. Weiss, J. M., Kilts, C. D. Animal models of depression and schizophrenia. Textbook of Psychopharmacology. , 89-131 (1998).
  33. Armario, A., Gavaldà, A., Martí, J. Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology. 20, 879-890 (1995).
  34. Paré, W. P. Open field, learned helplessness, conditioned defensive burying, and forced-swim tests in WKY rats. Physiology and Behavior. 55, 433-439 (1994).
  35. Overstreet, D. H., Friedman, E., Mathe, A. A., Yadid, G. The Flinders Sensitive Line rat: a selectively bred putative animal model of depression. Neuroscience and biobehavioral reviews. 29, 739-759 (2005).
  36. Piras, G., Piludu, M. A., Giorgi, O., Corda, M. G. Effects of chronic antidepressant treatments in a putative genetic model of vulnerability (Roman low-avoidance rats) and resistance (Roman high-avoidance rats) to stress-induced depression. Psychopharmacology. 231, 43-53 (2014).
  37. Bielajew, C., et al. Strain and Gender Specific Effects in the Forced Swim Test. Effects of Previous Stress Exposure. Stress. 6, 269-280 (2003).
  38. Fujisaki, C., et al. An immnosuppressive drug, cyclosporine-A acts like anti-depressant for rats under unpredictable chronic stress. Journal of Medical and Dental Sciences. 50, 93-100 (2003).
  39. Gomez, R., Vargas, C. R., Wajner, M., Barros, H. M. T. Lower in vivo brain extracellular GABA concentration in diabetic rats during forced swimming. Brain research. 968, 281-284 (2003).
  40. Hilakivi-Clarke, L. A., Wozniak, K. M., Durcan, M. J., Linnoila, M. Behavior of streptozotocin-diabetic mice in tests of exploration, locomotion, anxiety, depression and aggression. Physiology and Behavior. 48, 429-433 (1990).
  41. Cryan, J. F., Hoyer, D., Markou, A. Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biological psychiatry. 54, 49-58 (2003).
  42. Portella, M. J., et al. Can we really accelerate and enhance the selective serotonin reuptake inhibitor antidepressant effect? A randomized clinical trial and a meta-analysis of pindolol in nonresistant depression. The Journal of clinical psychiatry. 72, 962-969 (2011).
  43. Machado-Vieira, R., Salvadore, G., Luckenbaugh, D. A., Manji, H. K., Zarate, C. A. Rapid onset of antidepressant action: a new paradigm in the research and treatment of major depressive disorder. The Journal of clinical psychiatry. 69, 946-958 (2008).
  44. Bordet, R., Thomas, P., Dupuis, B. Effect of pindolol on onset of action of paroxetine in the treatment of major depression: intermediate analysis of a double-blind, placebo-controlled trial. Reseau de Recherche et d’Experimentation Psychopharmacologique. The American journal of psychiatry. 155, 1346-1351 (1998).
  45. Dulawa, S. C., Holick, K. A., Gundersen, B., Hen, R. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology. 29, 1321-1330 (2004).
  46. Willner, P. Animal models of depression: An overview. Pharmacology and Therapeutics. 45, 425-455 (1990).
  47. Jefferys, D., Funder, J. The effect of water temperature on immobility in the forced swimming test in rats. European Journal of Pharmacology. 253, 91-94 (1994).
  48. West, A. P. Neurobehavioral studies of forced swimming: The role of learning and memory in the forced swim test. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 14, 863-877 (1990).
  49. De Pablo, J. M., Parra, A., Segovia, S., Guillamon, A. Learned immobility explains the behavior of rats in the forced swimming test. Physiology and Behavior. 46, 229-237 (1989).
  50. Dal-Zotto, S., Martí, O., Armario, A. Influence of single or repeated experience of rats with forced swimming on behavioural and physiological responses to the stressor. Behavioural Brain Research. 114, 175-181 (2000).
  51. Rittenhouse, P. A., López-Rubalcava, C., Stanwood, G. D., Lucki, I. Amplified behavioral and endocrine responses to forced swim stress in the Wistar-Kyoto rat. Psychoneuroendocrinology. 27, 303-318 (2002).
  52. Overstreet, D. H., Keeney, A., Hogg, S. Antidepressant effects of citalopram and CRF receptor antagonist CP-154,526 in a rat model of depression. European Journal of Pharmacology. 492, 195-201 (2004).
  53. Chaki, S., et al. MGS0039: A potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology. 46, 457-467 (2004).
  54. Mague, S. D., et al. Antidepressant-like effects of κ-opioid receptor antagonists in the forced swim test in rats. Journal of Pharmacology and Experimental Therapeutics. 305, 323-330 (2003).
  55. Molina-Hernández, M., Téllez-Alcántara, N. P. Antidepressant-like actions of pregnancy, and progesterone in Wistar rats forced to swim. Psychoneuroendocrinology. 26, 479-491 (2001).
  56. Estrada-Camarena, E., Fernández-Guasti, A., López-Rubalcava, C. Antidepressant-like effect of different estrogenic compounds in the forced swimming test. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 28, 830-838 (2003).
  57. Gersner, R., Gordon-Kiwkowitz, M., Zangen, A. Automated behavioral analysis of limbs’ activity in the forced swim test. Journal of neuroscience. 180, 82-86 (2009).
  58. Einat, H. Partial effects of the protein kinase C inhibitor chelerythrine in a battery of tests for manic-like behavior in black Swiss mice. Pharmacological reports : PR. 66, 722-725 (2014).

Tags

Forced Swim TestDepressive-like BehaviorRodent ModelBehavioral DespairStressAntidepressant DrugsPredictive ValidityChronic AugmentationBrain Structure/function

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Yankelevitch-Yahav, R., Franko, M., Huly, A., Doron, R. The Forced Swim Test as a Model of Depressive-like Behavior. J. Vis. Exp. (97), e52587, doi:10.3791/52587 (2015).
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