Skip to main content

Behavioral Testing of Mice Concerning Anxiety and Depression

What Can We Learn From it?

Published Online:https://doi.org/10.1027/2151-2604/a000215

Abstract. In the development of new psychiatric drugs and the exploration of their efficacy, behavioral testing in mice has always shown to be an inevitable procedure. By studying the behavior of mice, diverse pathophysiological processes leading to depression, anxiety, and sickness behavior have been revealed. Moreover, laboratory research in animals increased at least the knowledge about the involvement of a multitude of genes in anxiety and depression. However, multiple new possibilities to study human behavior have been developed recently and improved and enable a direct acquisition of human epigenetic, imaging, and neurotransmission data on psychiatric pathologies. In human beings, the high influence of environmental and resilience factors gained scientific importance during the last years as the search for key genes in the development of affective and anxiety disorders has not been successful. However, environmental influences in human beings themselves might be better understood and controllable than in mice, where environmental influences might be as complex and subtle. The increasing possibilities in clinical research and the knowledge about the complexity of environmental influences and interferences in animal trials, which had been underestimated yet, question more and more to what extent findings from laboratory animal research translate to human conditions. However, new developments in behavioral testing of mice involve the animals’ welfare and show that housing conditions of laboratory mice can be markedly improved without affecting the standardization of results.

References

  • Bhattacharyha, R., Shen, C. & Sambamoorthi, U. (2014). Excess risk of chronic physical conditions associated with depression and anxiety. Biomedcentral Psychiatry, 14, 10. First citation in articleGoogle Scholar

  • Campos, A. C., Fogaca, M. V., Aguiar, D. C. & Guimaraes, F. S. (2013). Animal models of anxiety disorders and stress. Revista Brasileira de Psiquiatria, 35, S101–S111. First citation in articleGoogle Scholar

  • Can, A., Dao, D. T., Terrillion, C. E., Piantadosi, S. C., Bhat, S. & Gould, T. D. (2012). The tail suspension test. Journal of Visualized Experiments, 59, 3769. First citation in articleGoogle Scholar

  • Charney, D. S. (2004). Psychobiological mechanisms of resilience and vulnerability: Implications for successful adaptation to extreme stress. The American Journal of Psychiatry, 161, 195–216. First citation in articleCrossrefGoogle Scholar

  • Crabbe, J. C. & Morris, R. G. (2004). Festina lente: Late-night thoughts on high-throughput screening of mouse behavior. Nature Neuroscience, 7, 1175–1179. First citation in articleCrossrefGoogle Scholar

  • Crawley, J. & Goodwin, F. K. (1980). Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacology Biochemistry and Behavior, 13, 167–170. First citation in articleCrossrefGoogle Scholar

  • Cryan, J. F., Mombereau, C. & Vassout, A. (2005). The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice. Neuroscience & Biobehavioral Reviews, 29, 571–625. First citation in articleCrossrefGoogle Scholar

  • Dulawa, S. C., Grandy, D. K., Low, M. J., Paulus, M. P. & Geyer, M. A. (1999). Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. The Journal of Neuroscience, 19, 9550–9556. First citation in articleGoogle Scholar

  • Green, R. C., Cupples, L. A., Kurz, A., Auerbach, S., Go, R., Sadovnick, D., … Farrer, L. (2003). Depression as a risk factor for Alzheimer disease: The MIRAGE study. Archives of Neurology, 60, 753–759. First citation in articleCrossrefGoogle Scholar

  • Griebel, G., Rodgers, R. J., Perrault, G. & Sanger, D. J. (1997). Risk assessment behaviour: Evaluation of utility in the study of 5-HT-related drugs in the rat elevated plus-maze test. Pharmacology Biochemistry and Behavior, 57, 817–827. First citation in articleCrossrefGoogle Scholar

  • Hall, C. S. (1934). Emotional behavior of the rat. Defecation and urination as measures of the individual differences in emotionality. Journal of Comparative Psychology, 18, 385–403. First citation in articleCrossrefGoogle Scholar

  • Handley, S. L. & Mithani, S. (1984). Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of “fear”-motivated behaviour. Naunyn Schmiedebergs Archives of Pharmacology, 327, 1–5. First citation in articleCrossrefGoogle Scholar

  • Hesdorffer, D. C., Hauser, W. A., Annegers, J. F. & Cascino, G. (2000). Major depression is a risk factor for seizures in older adults. Annals of Neurology, 47, 246–249. First citation in articleCrossrefGoogle Scholar

  • Kalueff, A. V., Wheaton, M. & Murphy, D. L. (2007). What’s wrong with my mouse model? Advances and strategies in animal modeling of anxiety and depression. Behavioural Brain Research, 179, 1–18. First citation in articleCrossrefGoogle Scholar

  • Kõks, S., Beljajev, S., Koovit, I., Abramov, U., Bourin, M. & Vasar, E. (2001). 8-OH-DPAT, but not deramciclane, antagonizes the anxiogenic-like action of paroxetine in an elevated plus-maze. Psychopharmacology (Berl), 153, 365–372. First citation in articleCrossrefGoogle Scholar

  • Krishnan, V. & Nestler, E. J. (2010). Linking molecules to mood: New insight into the biology of depression. The American Journal of Psychiatry, 167, 1305–1320. First citation in articleCrossrefGoogle Scholar

  • Lang, U. E. & Borgwardt, S. (2013). Molecular mechanisms of depression: Perspectives on new treatment strategies. Cellular Physiology and Biochemistry, 31, 761–777. First citation in articleCrossrefGoogle Scholar

  • Lang, U. E., Wolfer, D. P., Grahammer, F., Strutz-Seebohm, N., Seebohm, G., Lipp, H. P., Dawson, K., … Lang, F. (2006). Reduced locomotion in the serum and glucocorticoid inducible kinase 3 knock out mouse. Behavioural Brain Research, 167, 75–86. First citation in articleCrossrefGoogle Scholar

  • Leibrock, C., Ackermann, T. F., Hierlmeier, M., Lang, F., Borgwardt, S. & Lang, U. E. (2013). Akt2 deficiency is associated with anxiety and depressive behaviour in mice. Cellular Physiology and Biochemistry, 32, 766–777. First citation in articleCrossrefGoogle Scholar

  • Madani, R., Kozlov, S., Akhmedov, A., Cinelli, P., Kinter, J., Lipp, H. P., … Wolfer, D. P. (2003). Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin. Molecular and Cellular Neuroscience, 23, 473–494. First citation in articleCrossrefGoogle Scholar

  • Maier, S. F. (1984). Learned helplessness and animal models of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 8, 435–446. First citation in articleCrossrefGoogle Scholar

  • Mathers, C. D. & Loncar, D. (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 3(11), e442. First citation in articleCrossrefGoogle Scholar

  • Montgomery, K. C. (1958). The relation between fear induced by novel stimulation and exploratory behaviour. Journal of Comparative and Physiological Psychology, 48, 254–260. First citation in articleCrossrefGoogle Scholar

  • Nouwen, A., Lloyd, C. E. & Pouwer, F. (2009). Depression and type 2 diabetes over the lifespan: A meta-analysis. Response to Mezuk et al. Diabetes Care, 32, 56–57. First citation in articleCrossrefGoogle Scholar

  • Padovan, C. M. & Guimaraes, F. S. (2000). Restraint-induced hypoactivity in an elevated plus-maze. Brazilian Journal of Medical and Biological Research, 33, 79–83. First citation in articleCrossrefGoogle Scholar

  • Pellow, S. & File, S. E. (1986). Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacology Biochemistry and Behavior, 24, 525–529. First citation in articleCrossrefGoogle Scholar

  • Penninx, B. W., Guralnik, J. M., Pahor, M., Ferrucci, L., Cerhan, J. R., Wallace, R. B. & Havlik, R. J. (1998). Chronically depressed mood and cancer risk in older persons. Journal of the National Cancer Institute, 90, 1888–1893. First citation in articleCrossrefGoogle Scholar

  • Phillips, T. J., Belknap, J. K., Hitzemann, R. J., Buck, K. J., Cunningham, C. L. & Crabbe, J. C. (2002). Harnessing the mouse to unravel the genetics of human disease. Genes, Brain and Behavior, 1, 14–26. First citation in articleCrossrefGoogle Scholar

  • Poltronieri, S. C., Zangrossi, H. Jr. & de Barros Viana, M. (2003). Antipanic-like effect of serotonin reuptake inhibitors in the elevated T-maze. Behavioural Brain Research, 147, 185–192. First citation in articleCrossrefGoogle Scholar

  • Porsolt, R. D. (2000). Animal models of depression: Utility for transgenic research. Reviews Neuroscience, 11, 53–58. First citation in articleGoogle Scholar

  • Porsolt, R. D., Le Pichon, M. & Jalfre, M. (1977). Depression: A new animal model sensitive to antidepressant treatments. Nature, 266, 730–732. First citation in articleCrossrefGoogle Scholar

  • Prickaerts, J., Moechars, D., Cryns, K., Lenaerts, I., van Craenendonck, H., Goris, I., … Steckler, T. (2006). Transgenic mice overexpressing glycogen synthase kinase 3beta: A putative model of hyperactivity and mania. The Journal of Neuroscience, 26, 9022–9029. First citation in articleCrossrefGoogle Scholar

  • Ramasubbu, R. & Patten, S. B. (2003). Effect of depression on stroke morbidity and mortality. Canadian Journal of Psychiatry, 48, 250–257. First citation in articleGoogle Scholar

  • Schmidt, M. V. (2011). Animal models for depression and the mismatch hypothesis of disease. Psychoneuroendocrinology, 36, 330–338. First citation in articleCrossrefGoogle Scholar

  • Scott, K. M., Bruffaerts, R., Tsang, A., Ormel, J., Alonso, J., Angermeyer, M. C., … Von Korff, M. (2007). Depression-anxiety relationships with chronic physical conditions: Results from the World Mental Health Surveys. Journal of Affective Disorders, 103, 113–120. First citation in articleCrossrefGoogle Scholar

  • Steru, L., Chermat, R., Thierry, B. & Simon, P. (1985). The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl), 85, 367–370. First citation in articleCrossrefGoogle Scholar

  • Teixeira, R. C., Zangrossi, H. & Graeff, F. G. (2000). Behavioral effects of acute and chronic imipramine in the elevated T-maze model of anxiety. Pharmacology Biochemistry and Behavior, 65, 571–576. First citation in articleCrossrefGoogle Scholar

  • Van der Kooy, K., van Hout, H., Marwijk, H., Marten, H., Stehouwer, C. & Beekman, A. (2007). Depression and the risk for cardiovascular diseases: Systematic review and meta-analysis. International Journal of Geriatric Psychiatry, 22, 613–626. First citation in articleCrossrefGoogle Scholar

  • Vannoni, E., Voikar, V., Colacicco, G., Sánchez, M. A., Lipp, H. P. & Wolfer, D. P. (2014). Spontaneous behavior in the social homecage discriminates strains, lesions and mutations in mice. Journal of Neuroscience Methods, 234, 26–37. First citation in articleCrossrefGoogle Scholar

  • Vollmayr, B. & Gass, P. (2013). Learned helplessness: Unique features and translational value of a cognitive depression model. Cell and Tissue Research, 354, 171–178. First citation in articleCrossrefGoogle Scholar

  • Wahlsten, D., Bachmanov, A., Finn, D. A. & Crabbe, J. C. (2006). Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades. Proceedings of the National Academy of Sciences of the United States of America, 103, 16364–16369. First citation in articleCrossrefGoogle Scholar

  • Whishaw, I. Q., Gharbawie, O. A., Clark, B. J. & Lehmann, H. (2006). The exploratory behavior of rats in an open environment optimizes security. Behavioural Brain Research, 171, 230–239. First citation in articleCrossrefGoogle Scholar

  • Wolfer, D. P., Litvin, O., Morf, S., Nitsch, R. M., Lipp, H. P. & Würbel, H. (2004). Laboratory animal welfare: Cage enrichment and mouse behaviour. Nature, 432, 821–822. First citation in articleCrossrefGoogle Scholar