Rodent Models of Depression: Forced Swim and Tail Suspension Behavioral Despair Tests in Rats and Mice

Vincent Castagné1, Paul Moser1, Sylvain Roux1, Roger D. Porsolt1

1 Porsolt & Partners Pharmacology, Boulogne‐Billancourt, France
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 8.10A
DOI:  10.1002/0471142301.ns0810as55
Online Posting Date:  April, 2011
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant‐like activity. The behavioral despair and the tail suspension tests are based on the same principle: measurement of the duration of immobility when rodents are exposed to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Antidepressants also increase the latency to immobility, and this additional measure can increase the sensitivity of the behavioral despair test in the mouse for certain classes of antidepressant. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility. Curr. Protoc. Neurosci. 55:8.10A.1‐8.10A.14. © 2011 by John Wiley & Sons, Inc.

Keywords: animal models; antidepressants; behavior; depression; mice; rats

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Forced Swim (Behavioral Despair) Test in the Rat
  • Alternate Protocol 1: Forced Swim (Behavioral Despair) Test in the Mouse
  • Alternate Protocol 2: Tail Suspension Test in the Mouse
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Forced Swim (Behavioral Despair) Test in the Rat

  Materials
  • 180‐ to 280‐g male Wistar rats (e.g., Elevage Janvier)
  • Standard rodent diet
  • Treatment solutions (see recipe): drug or test compound, reference compound (e.g., imipramine hydrochloride, Sigma or equivalent), and vehicle alone (for control)
  • Transparent plastic cages (e.g., Macrolon 44 × 28 × 19‐cm), containing wood shavings (e.g., Litalabo, SPPS, http://www.sppsfrance.com)
  • Transparent Plexiglas cylinders (20 cm diameter × 40 cm high) containing water (25°C ± 2°C) to a depth of 13 cm (made in house or obtained from commercial suppliers of Plexiglas material)
  • Opaque screens for separating cylinders
  • Metric balance (e.g., Sartorius model 1401.001.2), accurate to 1 g
  • 2‐ml syringes for intraperitoneal and subcutaneous injections (e.g., Terumo type BS‐025)
  • 23‐G × 1‐in. (0.6 × 16‐mm) needles for intraperitoneal injections (e.g., Terumo)
  • 21‐G × 1.5‐in. (0.8 × 40‐mm) needles for subcutaneous injections (e.g., Terumo)
  • Luer gastric probes with oval extremity (70 mm long × 1.5 mm oval diameter) for oral administration

Alternate Protocol 1: Forced Swim (Behavioral Despair) Test in the Mouse

  Materials
  • 20‐ to 25‐g male NMRI (Naval Medical Research Institute) mice (e.g., Elevage Janvier)
  • Standard rodent diet
  • Treatment solutions (see recipe): drug or test compound, reference compound (e.g., imipramine hydrochloride, Sigma or equivalent), and vehicle alone (for control)
  • Transparent plastic cages (e.g., type Macrolon 25 × 19 × 13 cm) containing wood shavings (e.g., Litalabo, SPPS, http://www.sppsfrance.com)
  • Transparent Plexiglas cylinders (13 cm diameter × 24 cm high) containing water (22°C ± 2°C) to a depth of 10 cm (made in‐house or obtained from commercial suppliers of Plexiglas material)
  • Opaque screens for separating cylinders
  • Metric balance (e.g., Sartorius type 1401.001), accurate to 0.1 g
  • 1‐ml syringes (e.g., Terumo type BS‐01‐T)
  • 25‐G × 0.625‐in. (0.5 × 16–mm) needles for intraperitoneal injections (e.g., Terumo)
  • 23‐G × 1‐in. (0.6 × 25–mm) needles for subcutaneous injections (e.g., Terumo)
  • Luer gastric probes with oval extremity (25 mm long × 1.2 mm oval diameter) for oral administration

Alternate Protocol 2: Tail Suspension Test in the Mouse

  Materials
  • 20‐ to 25‐g male Swiss or NMRI mice (e.g., Elevage Janvier)
  • Standard rodent diet
  • Treatment solutions (see recipe): drug or test compound, reference compounds (e.g., imipramine hydrochloride and diazepam, Sigma or equivalent), and vehicle alone (for control)
  • Transparent plastic cages (e.g., Macrolon 25 cm × 19 cm × 13 cm) containing wood shavings (e.g., Litalabo, SPPS, http://www.sppsfrance.com)
  • Automated tail suspension apparatus (e.g., TST System; Bioseb, http://www.bioseb.com) consisting of plastic enclosures (20 cm × 25 cm × 30 cm) fitted with a ceiling hook connected to a strain gauge and computer assembly with Windows compatible software
  • Metric balance (e.g., Sartorius type 1101601), accurate to 0.1 g
  • 1‐ml syringes (e.g., Terumo type BS‐01‐T)
  • 25‐G × 0.625‐in. (0.5 × 16‐mm) needles for intraperitoneal injections (e.g., Terumo)
  • 23‐G × 1‐in. (0.6 × 25‐mm) needles for subcutaneous injections (e.g., Terumo)
  • Luer gastric probes with oval extremity (25‐mm long × 1.2‐mm oval diameter) for oral administration
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Baghai, T.C., Volz, H.P., and Moller, H.J. 2006. Drug treatment of depression in the 2000s: An overview of achievements in the last 10 years and future possibilities. World J. Biol. Psychiatry 7:198‐222.
   Berton, O. and Nestler, E.J. 2006. New approaches to antidepressant drug discovery: Beyond the monoanines. Nat. Rev. Neurosci. 7:137‐151.
   Borsini, F. and Meli, A. 1988. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 94:147‐161.
   Bosker, F.J., Westerink, B.H., Cremers, T.I., Gerrits, M., van der Hart, M.G., Kuipers, S.D., van der Horst, P.G., den Boer, J.A., and Korf, J. 2004. Future antidepressants: what is in the pipeline and what is missing? CNS Drugs 18:705‐732.
   Candy, M., Jones, L., Williams, R., Tookman, A., and King, M. 2008. Psychostimulants for depression. Cochrane Database Syst. Rev. 2:CD006722.
   Carlezon, W.A., Pliakas, A.M., Parow, A.M., Detke, M.J., Cohen, B.M. and Renshaw, P.F. 2002. Antidepressant‐like effects of cytidine in the forced swim test in rats. Biol. Psychiatry 51:882‐889.
   Castagné, V., Porsolt, R.D., and Moser, P. 2006. Early behavioral screening for antidepressants and anxiolytics. Drug Dev. Res. 67:729‐742.
   Castagné, V., Porsolt, R.D., and Moser, P. 2009. Use of latency to immobility improves detection of antidepressant‐like activity in the behavioral despair test in the mouse. Eur. J. Pharmacol. 616:128‐133.
   Contreras, C.M., Rodriguez‐Landa, J.F., Guttierez‐Garcia, A.G., and Bernal‐Morales, B. 2001. The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of laperel septal nucleus neurones in the rat. J. Psychopharmacol. 15:231‐236.
   Cryan, J.F., Mombereau, C., and Vassout, A. 2005. The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice. Neurosci. Biobehav. Rev. 29:571‐625.
   Dalvi, A. and Lucki, I. 1999. Murine models of depression. Psychopharmacology 147:14‐16.
   David, D.J., Renard, C.E., Jolliet, P., Hascoët, M., and Bourin, M. 2003. Antidepressant‐like effects in various mice strains in the forced swimming test. Psychopharmacology 166:373‐382.
   Detke, M.J. and Lucki, I. 1996. Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: The effects of water depth. Behav. Brain Res. 73:43‐46.
   Harlow, H.F. and Suomi, S.F. 1974. Induced depression in monkeys. Behav. Biol. 12:273‐296.
   Lahmame, A. and Armario, A. 1995. Differential responsiveness of inbred strains of rats to antidepressant treatment in the forced swimming test: Are Wistar Kyoto rats an animal model of subsensitivity to antidepressants? Psychopharmacology 123:191‐198.
   Lopez‐Rubalcava, C. and Lucki, I. 2000. Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology 22:191‐199.
   Matthews, K., Christmas, D., Swan, J., and Sorell, E. 2005. Animal models of depression: Navigating through the clinical fog. Neurosci. Biobehav. Rev. 29:503‐513.
   Overstreet, D.H., Rezvani, A.H., and Janowsky, D.S. 1992. Maudsley reactive and nonreactive rats differ only in some tasks reflecting emotionality. Physiol. Behav. 52:149‐152.
   Petit‐Demouliere, B., Chenu, F., and Bourin, M. 2005. Forced swimming test in mice: A review of antidepressant activity. Psychopharmacology 177:245‐255.
   Porsolt, R.D., Le Pichon, M., and Jalfre, M. 1977. Depression: A new animal model sensitive to antidepressant treatment. Nature 266:730‐732.
   Porsolt, R.D., Bertin, A., and Jalfre, M. 1978. Behavioural despair in rats and mice: Strain differences and the effects of imipramine. Eur. J. Pharmacol. 51:291‐294.
   Porsolt, R.D., Deniel, M., and Jalfre, M. 1979. Forced swimming in rats: Hypothermia, immobility and the effects of imipramine. Eur. J. Pharmacol. 57:431‐436.
   Porsolt, R.D., Chermat, R., Lenegre, A., Avril, I., Janvier, S., and Stéru, L. 1987. Use of the automated tail suspension test for the primary screening of psychotropic agents. Arch. Int. Pharmacodyn. Ther. 288:11‐30.
   Porsolt, R.D., Lenegre, A., and McArthur, R.A. 1991. Pharmacological models of depression. In Animal Models in Psychopharmacology (B. Olivier, J. Mos, and J.L. Slangen, eds.) pp. 137‐160. Birkhauser Verlag, Basel.
   Seligman, M.E.P. 1975. Helplessness: On Depression Development and Death. W.H. Freeman, San Francisco.
   Slattery, D.A., Hudson, A.L., and Nutt, D.J., 2004. Invited review: The evolution of antidepressant mechanisms. Fundam. Clin. Pharmacol. 18:1‐21.
   Stéru, L., Chermat, R., Thierry, B., and Simon, P. 1985. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology 85:367‐370.
   Stéru, L., Chermat, R., Thierry, B., Mico, J‐A., Lenegre, A., Stéru, M., Simon, P., and Porsolt, R.D., 1987. The automated tail suspension test: A computerized device which differentiates psychotropic drugs. Prog. Neuropsychopharmacol. Biol. Psychiatry 11:659‐671.
   Vaugeois, J.M., Odievre, C., Laisel, L., and Costentin, J., 1996. A genetic model of helplessness sensitive to imipramine. Eur. J. Pharmacol. 361:R1‐R2.
   Vazquez‐Palacios, G., Bonilla‐Jaime, H., and Velazquez‐Moctezuma, J. 2004. Antidepressant‐like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine. Pharmacol. Biochem. Behav. 78:165‐169.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library