Plasticity and AnxietyView this Special Issue
Research Article | Open Access
Anxiety in Mice: A Principal Component Analysis Study
Two principal component analyses of anxiety were undertaken investigating two strains of mice (ABP/Le and C57BL/6ByJ) in two different experiments, both classical tests for assessing anxiety in rodents. The elevated plus-maze and staircase were used for the first experiment, and a free exploratory paradigm and light-dark discrimination were used for the second. The components in the analyses produced definitions of four fundamental behavior patterns: novelty-induced anxiety, general activity, exploratory behavior, and decision making. We also noted that the anxious phenotype was determined by both strain and experimental procedure. The relationship between behavior patterns and the use of specific tests plus links with the genetic background are discussed.
- J. N. Crawley and F. K. Goodwin, “Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines,” Pharmacology Biochemistry and Behavior, vol. 13, no. 2, pp. 167–170, 1980.
- R. J. Rodgers, B. J. Cao, A. Dalvi, and A. Holmes, “Animal models of anxiety: an ethological perspective,” Brazilian Journal of Medical and Biological Research, vol. 30, no. 3, pp. 289–304, 1997.
- C. Sánchez, “5- receptors play an important role in modulation of behavior of rats in a two-compartment black and white box,” Behavioural Pharmacology, vol. 7, no. 8, pp. 788–797, 1996.
- G. Griebel, C. Belzung, R. Misslin, and E. Vogel, “The free-exploratory paradigm: an effective method for measuring neophobic behaviour in mice and testing potential neophobia-reducing drugs,” Behavioural Pharmacology, vol. 4, no. 6, pp. 637–644, 1993.
- T. Shimada, K. Matsumoto, M. Osanai, H. Matsuda, K. Terasawa, and H. Watanabe, “The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs,” General Pharmacology, vol. 26, no. 1, pp. 205–210, 1995.
- N. Andrews, S. Hogg, L. E. Gonzalez, and S. E. File, “5- receptors in the median raphe nucleus and dorsal hippocampus may mediate anxiolytic and anxiogenic behaviours respectively,” European Journal of Pharmacology, vol. 264, no. 3, pp. 259–264, 1994.
- C. Belzung, R. Misslin, E. Vogel, R. H. Dodd, and G. Chapouthier, “Anxiogenic effects of methyl--carboline-3-carboxylate in a light/dark choice situation,” Pharmacology Biochemistry and Behavior, vol. 28, no. 1, pp. 29–33, 1987.
- S. Pellow and S. E. File, “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, vol. 24, no. 3, pp. 525–529, 1986.
- R. J. Rodgers, J. C. Cole, M. R. Cobain et al., “Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus-maze: profile comparisons with 8-OH-DPAT, CGS 12066B, TFMPP and mCPP,” Behavioural Pharmacology, vol. 3, no. 6, pp. 621–634, 1992.
- DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association, Washington, DC, USA, 4th edition, 1994.
- A. Beuzen and C. Belzung, “Link between emotional memory and anxiety states: a study by principal component analysis,” Physiology and Behavior, vol. 58, no. 1, pp. 111–118, 1995.
- R. Landgraf and A. Wigger, “Born to be anxious: neuroendocrine and genetic correlates of trait anxiety in HAB rats,” Stress, vol. 6, no. 2, pp. 111–119, 2003.
- R. G. Lister, “Ethologically-based animal models of anxiety disorders,” Pharmacology and Therapeutics, vol. 46, no. 3, pp. 321–340, 1990.
- C. Belzung and G. Griebel, “Measuring normal and pathological anxiety-like behaviour in mice: a review,” Behavioural Brain Research, vol. 125, no. 1-2, pp. 141–149, 2001.
- T. L. Doremus, E. I. Varlinskaya, and L. P. Spear, “Factor analysis of elevated plus-maze behavior in adolescent and adult rats,” Pharmacology Biochemistry and Behavior, vol. 83, no. 4, pp. 570–577, 2006.
- C. Gross, L. Santarelli, D. Brunner, X. Zhuang, and R. Hen, “Altered fear circuits in 5- receptor KO mice,” Biological Psychiatry, vol. 48, no. 12, pp. 1157–1163, 2000.
- K. Kanari, T. Kikusui, Y. Takeuchi, and Y. Mori, “Multidimensional structure of anxiety-related behavior in early-weaned rats,” Behavioural Brain Research, vol. 156, no. 1, pp. 45–52, 2005.
- Y. S. Mineur, C. Belzung, and W. E. Crusio, “Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice,” Behavioural Brain Research, vol. 175, no. 1, pp. 43–50, 2006.
- Y. S. Mineur and W. E. Crusio, “Behavioral and neuroanatomical characterization of FVB/N inbred mice,” Brain Research Bulletin, vol. 57, no. 1, pp. 41–47, 2002.
- Y. S. Mineur, F. Sluyter, S. de Wit, B. A. Oostra, and W. E. Crusio, “Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse,” Hippocampus, vol. 12, no. 1, pp. 39–46, 2002.
- R. C. Shelton and L. L. Brown, “Mechanisms of action in the treatment of anxiety,” Journal of Clinical Psychiatry, vol. 62, 12, pp. 10–15, 2001.
- Y. Clément, F. Calatayud, and C. Belzung, “Genetic basis of anxiety-like behaviour: a critical review,” Brain Research Bulletin, vol. 57, no. 1, pp. 57–71, 2002.
- W. E. Crusio, H. Schwegler, I. Brust, and J. H. F. Van Abeelen, “Genetic selection for novelty-induced rearing behavior in mice produces changes in hippocampal mossy fiber distributions,” Journal of Neurogenetics, vol. 5, no. 1, pp. 87–93, 1989.
- J. A. Gordon and R. Hen, “Genetic approaches to the study of anxiety,” Annual Review of Neuroscience, vol. 27, pp. 193–222, 2004.
- H. Imada, “Emotional reactivity and conditionability in four strains of rats,” Journal of Comparative and Physiological Psychology, vol. 79, no. 3, pp. 474–480, 1972.
- D. F. Peeler and R. S. Nowakowski, “Genetic factors and the measurement of exploratory activity,” Behavioral and Neural Biology, vol. 48, no. 1, pp. 90–103, 1987.
- J. Streng, “Open-field behavior in four inbred mouse strains,” Canadian Journal of Psychology, vol. 25, no. 1, pp. 62–68, 1971.
- Y. Clément, C. Adelbrecht, B. Martin, and G. Chapouthier, “Association of autosomal loci with the grooming activity in mice observed in open-field,” Life Sciences, vol. 55, no. 22, pp. 1725–1734, 1994.
- Y. Clément, B. Martin, P. Venault, and G. Chapouthier, “Involvement of regions of the 4th and 7th chromosomes in the open-field activity of mice,” Behavioural Brain Research, vol. 70, no. 1, pp. 51–57, 1995.
- Y. Clément and G. Chapouthier, “Biological bases of anxiety,” Neuroscience and Biobehavioral Reviews, vol. 22, no. 5, pp. 623–633, 1998.
- R. G. Lister, “The use of a plus-maze to measure anxiety in the mouse,” Psychopharmacology, vol. 92, no. 2, pp. 180–185, 1987.
- A. P. M. Cruz, F. Frei, and F. G. Graeff, “Ethopharmacological analysis of rat behavior on the elevated plus-maze,” Pharmacology Biochemistry and Behavior, vol. 49, no. 1, pp. 171–176, 1994.
- R. J. Rodgers and N. J. T. Johnson, “Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety,” Pharmacology Biochemistry and Behavior, vol. 52, no. 2, pp. 297–303, 1995.
- J. Simiand, P. E. Keane, and M. Morre, “The staircase test in mice: a simple and efficient procedure for primary screening of anxiolytic agents,” Psychopharmacology, vol. 84, no. 1, pp. 48–53, 1984.
- E. M. Lepicard, C. Joubert, I. Hagneau, F. Perez-Diaz, and G. Chapouthier, “Differences in anxiety-related behavior and response to diazepam in BALB/cByJ and C57BL/6J strains of mice,” Pharmacology Biochemistry and Behavior, vol. 67, no. 4, pp. 739–748, 2000.
- C. Florio, A. Prezioso, A. Papaioannou, and R. Vertua, “Adenosine receptors modulate anxiety in CD1 mice,” Psychopharmacology, vol. 136, no. 4, pp. 311–319, 1998.
- C. Belzung and F. Berton, “Further pharmacological validation of the BALB/c neophobia in the free exploratory paradigm as an animal model of trait anxiety,” Behavioural Pharmacology, vol. 8, no. 6-7, pp. 541–548, 1997.
- L. Stéru, B. Thierry, R. Chermat, B. Millet, P. Simon, and R. D. Porsolt, “Comparing benzodiazepines using the staircase test in mice,” Psychopharmacology, vol. 92, no. 1, pp. 106–109, 1987.
- M. H. Thiébot, P. Soubrié, P. Simon, and J. R. Boissier, “Dissociation of two components of rat behaviour by psychotropic drugs. Utilization for studying anxiolytic drugs,” Psychopharmacologia, vol. 31, no. 1, pp. 77–90, 1973.
- J. N. Crawley, “Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines,” Pharmacology Biochemistry and Behavior, vol. 15, no. 5, pp. 695–699, 1981.
- G. Griebel, C. Belzung, G. Perrault, and D. J. Sanger, “Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice,” Psychopharmacologia, vol. 148, no. 2, pp. 164–170, 2000.
- E. F. Espejo, “Effects of weekly or daily exposure to the elevated plus-maze in male mice,” Behavioural Brain Research, vol. 87, no. 2, pp. 233–238, 1997.
- S. Pellow, P. Chopin, S. E. File, and M. Briley, “Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat,” Journal of Neuroscience Methods, vol. 14, no. 3, pp. 149–167, 1985.
- C. Belzung and G. Le Pape, “Comparison of different behavioral test situations used in psychopharmacology for measurement of anxiety,” Physiology and Behavior, vol. 56, no. 3, pp. 623–628, 1994.
- H. Takeda, M. Tsuji, and T. Matsumiya, “Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice,” European Journal of Pharmacology, vol. 350, no. 1, pp. 21–29, 1998.
- G. Griebel, G. Perrault, and D. J. Sanger, “CCK receptor antagonists in animal models of anxiety: comparison between exploration tests, conflict procedures and a model based on defensive behaviours,” Behavioural Pharmacology, vol. 8, no. 6-7, pp. 549–560, 1997.
- Y. Lamberty and A. J. Gower, “Arm width and brightness modulation of spontaneous behaviour of two strains of mice tested in the elevated plus-maze,” Physiology and Behavior, vol. 59, no. 3, pp. 439–444, 1996.
- C. Mathis, S. M. Paul, and J. N. Crawley, “Characterization of benzodiazepine-sensitive behaviors in the A/J and C57BL/6J inbred strains of mice,” Behavior Genetics, vol. 24, no. 2, pp. 171–180, 1994.
- C. Vadasz, G. Kobor, and A. Lajtha, “Motor activity and the mesotelencephalic dopamine function. I. High-resolution temporal and genetic analysis of open-field behavior,” Behavioural Brain Research, vol. 48, no. 1, pp. 29–39, 1992.
- A. Ågmo, R. Pruneda, M. Guzmán, and M. Gutiérrez, “GABAergic drugs and conflict behavior in the rat: lack of similarities with the actions of benzodiazepines,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 344, no. 3, pp. 314–322, 1991.
- C. Belzung and D. Dubreuil, “Naloxone potentiates the anxiolytic but not the amnestic action of chlordiazepoxide in C57BL/6 mice,” Behavioural Pharmacology, vol. 9, no. 8, pp. 691–698, 1998.
- C. Belzung, A. M. Le Guisquet, and F. Crestani, “Flumazenil induces benzodiazepine partial agonist-like effects in BALB/c but not C57BL/6 mice,” Psychopharmacology, vol. 148, no. 1, pp. 24–32, 2000.
- A. Dalvi and R. J. Rodgers, “GABAergic influences on plus-maze behaviour in mice,” Psychopharmacology, vol. 128, no. 4, pp. 380–397, 1996.
- P. Simon, R. Dupuis, and J. Costentin, “Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions,” Behavioural Brain Research, vol. 61, no. 1, pp. 59–64, 1994.
- J. H. F. Van Abeelen, “Genetic analysis of locomotor activity in immature mice from two inbred strains,” Behavioral and Neural Biology, vol. 27, no. 2, pp. 214–217, 1979.
- R. J. Rodgers, J. C. Cole, K. Aboualfa, and L. H. Stephenson, “Ethopharmacological analysis of the effects of putative ‘anxiogenic’ agents in the mouse elevated plus-maze,” Pharmacology Biochemistry and Behavior, vol. 52, no. 4, pp. 805–813, 1995.
- R. M. Teixeira, A. R. S. Santos, S. J. Ribeiro, J. B. Calixto, G. A. Rae, and T. C. M. De Lima, “Effects of central administration of tachykinin receptor agonists and antagonists on plus-maze behavior in mice,” European Journal of Pharmacology, vol. 311, no. 1, pp. 7–14, 1996.
- Y. Clément, B. Martin, P. Venault, and G. Chapouthier, “Mouse chromosome 9 involvement in -CCM-induced seizures,” NeuroReport, vol. 7, no. 13, pp. 2226–2230, 1996.
- M. L. Rise, W. N. Frankel, J. M. Coffin, and T. N. Seyfried, “Genes for epilepsy mapped in the mouse,” Science, vol. 253, no. 5020, pp. 669–673, 1991.
- J. C. Crabbe, D. Wahlsten, and B. C. Dudek, “Genetics of mouse behavior: interactions with laboratory environment,” Science, vol. 284, no. 5420, pp. 1670–1672, 1999.
- W. E. Crusio, “Gene-targeting studies: new methods, old problems,” Trends in Neurosciences, vol. 19, no. 5, pp. 186–187, 1996.
- H. K. Gershenfeld and S. M. Paul, “Towards a genetics of anxious temperament: from mice to men,” Acta Psychiatrica Scandinavica. Supplement, vol. 98, no. 393, pp. 56–65, 1998.
- R. Plomin, M. J. Owen, and P. McGuffin, “The genetic basis of complex human behaviors,” Science, vol. 264, no. 5166, pp. 1733–1739, 1994.
Copyright © 2007 Yan Clément et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.