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Animal Models of Depression

  • Eva González-Trujano
  • Fabiola Domínguez
  • Juan Manuel Gallardo
  • Christian Guerra-Araiza
  • Julia J. Segura-Uribe
  • Sandra Orozco-SuárezEmail author
Chapter
  • 1.3k Downloads

Abstract

Stress is a concept related to biological responses produced in all living organisms when facing environmental changes. These biological responses allow them to adapt. Chronic stress is a major risk factor in the development of several chronic diseases that has a high social and economic impact in many countries. Within these diseases is depression. Through a better understanding of the neurobiology of stress and depressive episodes, better preventative therapies and antidepressants with fewer side effects may be developed. Animal models of chronic stress have provided very important information through the pathophysiology of depression-associated behaviors that are similar to the behavior of depressed patients. This chapter reviews several depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to the disease, validity and replicability, the molecular insights that they, and their capacity to offer the next generation of therapeutics for depression.

Keywords

Animal models Behavioral testing Depression Stress 

Notes

Acknowledgments

We would like to thank the CYTED program (Action 112RT0460. “CORNUCOPIA” thematic network) for the support to the accomplishment of this work.

References

  1. Abelaira HM, Réus GZ, Quevedo J. Animal models as tools to study the patho-physiology of depression. Rev Bras Psiquiatr. 2013;35(Suppl2):S112–20.CrossRefPubMedGoogle Scholar
  2. American Psychiatric Association. DSM-IV, diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: APA; 1994. p. 345–59.Google Scholar
  3. Armario A, Gavaldà A, Martí O. Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility, and defecation rate. Eur J Pharmacol. 1988;158:207–12.CrossRefPubMedGoogle Scholar
  4. Björkqvist K. Social defeat as a stressor in humans. Physiol Behav. 2001;73:435–42.CrossRefPubMedGoogle Scholar
  5. Blanchard DC, Blanchard RJ. Aggressive behavior in the rat. Behav Biol. 1977;21:197–224.CrossRefPubMedGoogle Scholar
  6. Blanchard DC, Blanchard RJ. Behavioral correlates of chronic dominance-subordination relationships of male rats in a seminatural situation. Neurosci Biobehav Rev. 1990;14:455–62.CrossRefPubMedGoogle Scholar
  7. Blanchard RJ, McKittrick CR, Blanchard DC. Animal models of social stress: effects on behavior and brain neurochemical systems. Physiol Behav. 2001;73:261–71.CrossRefPubMedGoogle Scholar
  8. Breslau N, Schultz L, Peterson E. Sex differences in depression: a role for preexisting anxiety. Psychiatr Res. 1995;58:1–12.CrossRefGoogle Scholar
  9. Cryan J, Holmes A. The ascent of mouse: advances in modeling human depression and anxiety. Nat Rev Drug Discov. 2005;4:775–90.CrossRefPubMedGoogle Scholar
  10. Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci. 2002;23:238–45.CrossRefPubMedGoogle Scholar
  11. Cryan JF, Valentino RJ, Lucki I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev. 2005a;29:547–69.CrossRefPubMedGoogle Scholar
  12. Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev. 2005b;29:571–625.CrossRefPubMedGoogle Scholar
  13. Dedic N, Walser SM, Deussing JM. Mouse models of depression. In: Uehara T, editor. Psychiatric disorders—trends and developments. Rijeka: InTech; 2011. p. 185–222.Google Scholar
  14. Del Cañizo LJF, López MD, Lledó GE, et al. Design of experimental models in surgical investigation. Actas Urol Esp. 2008;32:27–40.CrossRefGoogle Scholar
  15. Deussing JM. Animal models of depression. Drug Discov Today Dis Models. 2006;3:375–83.CrossRefGoogle Scholar
  16. Duman CH. Models of depression. Vitam Horm. 2010;82:1–22. doi: 10.1016/S0083-6729(10)82001-1.CrossRefPubMedGoogle Scholar
  17. Garner J. Stereotypies and other abnormal repetitive behaviors: potential impact on validity, reliability, and replicability of scientific outcomes. ILAR. 2005;46:106–17.CrossRefGoogle Scholar
  18. Gould T, Gottesman I. Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav. 2006;5:113–9.CrossRefPubMedGoogle Scholar
  19. Guimarães F, Joca S, Padovan C, Molina V. Mood disorders. In: Brandão M, Graeff F, editors. Neurobiology of mental disorders. New York, NY: Nova Science; 2006. p. 95–124.Google Scholar
  20. Henn FA, Edwards E, Anderson D, Vollmayr B. Psychotherapy and antidepressant treatment of depression: evidence for similar neurobiological mechanisms. World Psychiatry. 2002;1:115–7.PubMedPubMedCentralGoogle Scholar
  21. Insel TR. From animal models to model animals. Biol Psychiatry. 2007;62:1337–9.CrossRefPubMedGoogle Scholar
  22. Kelly JP, Wrynn AC, Leonard BE. The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther. 1997;74:299–316.CrossRefPubMedGoogle Scholar
  23. Knapman A, Heinzmann JM, Holsboer F, Landgraf R, Touma C. Modeling psychotic and cognitive symptoms of affective disorders: disrupted latent inhibition and reversal learning deficits in highly stress reactive mice. Neurobiol Learn Mem. 2010a;94:145–52.CrossRefPubMedGoogle Scholar
  24. Knapman A, Heinzmann JM, Hellweg R, Holsboer F, Landgraf R, Touma C. Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders. J Psychiatr Res. 2010b;44:566–75.CrossRefPubMedGoogle Scholar
  25. Krishnan V, Nestler EJ. Animal models of depression: molecular perspectives. Curr Top Behav Neurosci. 2011;7:121–47.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Kulkarni SK, Dhir A. Effect of various classes of antidepressants in behavioral paradigms of despair. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1248–54.CrossRefPubMedGoogle Scholar
  27. Langley G. The validity of animal experiments in medical research. Rev Semestr Droit Anim. 2009;1:161–8.Google Scholar
  28. Lieder F, Goodman ND, Huys QJM. Learned helplessness and generalization. Berlin: Paper presented at the cognitive science conference; 2013.Google Scholar
  29. Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol. 1997;8:523–32.CrossRefPubMedGoogle Scholar
  30. Maier SF, Watkins LR. Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci Biobehav Rev. 2005;29:829–41.CrossRefPubMedGoogle Scholar
  31. Martinez MM, Calvo-Torrent MA, Pico-Alfonso MA. Social defeat and subordination as models of social stress in laboratory rodents: a review. Aggress Behav. 1998;24:241–56.CrossRefGoogle Scholar
  32. Matthews K, Christmas D, Swan J, Sorrell E. Animal models of depression: navigating through the clinical fog. Neurosci Biobehav Rev. 2005;29:503–13.CrossRefPubMedGoogle Scholar
  33. Mayorga AJ, Lucki I. Limitations on the use of the C57BL/6 mouse in the tail suspension test. Psychopharmacology (Berl). 2001;155:110–2.CrossRefGoogle Scholar
  34. McKinney Jr WT, Bunney Jr WE. Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry. 1969;21:240–8.CrossRefPubMedGoogle Scholar
  35. Mesulam MM. Principles of behavioral and cognitive neurology. 2nd ed. New York, NY: Oxford University Press; 2000.Google Scholar
  36. Monleon S, D'Aquila P, Parra A, Simon VM, Brain PF, Willner P. Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine. Psychopharmacology (Berl). 1995;117:453–7.CrossRefGoogle Scholar
  37. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11:47–60.CrossRefPubMedGoogle Scholar
  38. Primeaux SD, Holmes PV. Role of aversively motivated behavior in the olfactory bulbectomy syndrome. Physiol Behav. 1999;67:41–7.CrossRefPubMedGoogle Scholar
  39. Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463:3–33.CrossRefPubMedGoogle Scholar
  40. Ripoll N, Paul David DJ, Dailly E, Hascoët M, Bourin M. Antidepressant-like effects in various mice strains in the tail suspension test. Behav Brain Res. 2003;143:193–200.CrossRefPubMedGoogle Scholar
  41. Ruiz JC, Soler MJ, Fuentes I, Tomás P. Intellectual functioning and memory deficits in schizophrenia. Compr Psychiatry. 2007;48:276–82.CrossRefPubMedGoogle Scholar
  42. Samsom JN, Wong AH. Schizophrenia and depression co-morbidity: what we have learned from animal models. Front Psychiatry. 2015;6:13.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Seligman ME, Beagley G. Learned helplessness in the rat. J Comp Physiol Psychol. 1975;88:534–41.CrossRefPubMedGoogle Scholar
  44. Sloman L. A new comprehensive evolutionary model of depression and anxiety. J Affect Disord. 2008;106:219–28.CrossRefPubMedGoogle Scholar
  45. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985;85:367–70.CrossRefGoogle Scholar
  46. Stock HS, Hand GA, Ford K, Wilson MA. Changes in defensive behaviors following olfactory bulbectomy in male and female rats. Brain Res. 2001;903:242–6.CrossRefPubMedGoogle Scholar
  47. Touma C, Fenzl T, Ruschel J, Palme R, Holsboer F, Kimura M, et al. Rhythmicity in mice selected for extremes in stress reactivity: behavioural, endocrine and sleep changes resembling endophenotypes of major depression. PLoS One. 2009;4, e4325.CrossRefPubMedPubMedCentralGoogle Scholar
  48. van der Staay FJ, Arndt SS, Nordquist RE. Evaluation of animal models of neurobehavioral disorders. Behav Brain Funct. 2009;5:11.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Vollmayr B, Henn FA. Learned helplessness in the rat: improvements in validity and reliability. Brain Res Protoc. 2001;8:1–7.CrossRefGoogle Scholar
  50. Vollmayr B, Bachteler D, Vengeliene V, Gass P, Spanagel R, Henn F. Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning. Behav Brain Res. 2004;150:217–21.CrossRefPubMedGoogle Scholar
  51. Wall PM, Messier C. Ethological confirmatory factor analysis of anxiety-like behaviour in the murine elevated plus-maze. Behav Brain Res. 2000;114:199–212.CrossRefPubMedGoogle Scholar
  52. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl). 1997;134:319–29.CrossRefGoogle Scholar
  53. Willner P. Chronic mild stress (CMS) revisited: consistency and behavioral-neurobiological concordance in the effects of CMS. Neuropsychobiology. 2005;52:90–110.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Eva González-Trujano
    • 1
  • Fabiola Domínguez
    • 2
  • Juan Manuel Gallardo
    • 3
  • Christian Guerra-Araiza
    • 4
  • Julia J. Segura-Uribe
    • 3
  • Sandra Orozco-Suárez
    • 3
    Email author
  1. 1.Dirección de Investigaciones en NeurocienciasInstituto Nacional de Psiquiatría Ramón de la Fuente MuñizMexicoMexico
  2. 2.Centro de Investigación Biomédica de OrienteInstituto Mexicano del Seguro SocialMetepecMexico
  3. 3.Unidad de Investigación Médica en Enfermedades Nefrológicas, Hospital de EspecialidadesCentro Médico Nacional, Siglo XXICiudad de MéxicoMexico
  4. 4.Unidad de Investigación Médica en Farmacología, Centro Médico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexicoMexico

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