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  • Print publication year: 2010
  • Online publication date: November 2010

14 - Animal models of anxiety disorders: behavioral and genetic approaches

from Section 3 - Understanding the causes of anxiety
Anxiety is both an innate and a constructed response to perceived and anticipated threat. This chapter explores anxiety as signal, symptom and syndrome, and describes the evolution of the major psychodynamic models of signal anxiety. The major psychodynamic models of signal anxiety posit anxiety as a signal of unconscious, intrapsychic danger. Neurobiological factors also contribute to the development and expression of anxiety symptoms and syndromes. Imaging techniques have been used to illustrate the presence of unconscious processes that to date have only been hypothesized; specifically that unconscious affects are a crucial determinant of behavior. Many symptomatic patients were forced to make adaptations to internal and external threats in early childhood. Ironically, the treatment of symptomatic anxiety may create an anxiety of its own, the anxiety about change. Many patients present with the acute onset of anxiety symptoms but do not meet the criteria for an Axis I anxiety disorder.
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Anxiety Disorders
  • Online ISBN: 9780511777578
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American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association.
Andreatini, R., Blanchard, C., Blanchard, R., et al. (2001). The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis. Brazilian Journal of Medical and Biological Research, 34, 145–154.
Arguello, P. A., & Gogos, J. A. (2006). Modeling madness in mice: one piece at a time. Neuron, 52, 179–196.
Belin, D., Mar, A. C., Dalley, J. W., Robbins, T. W., & Everitt, B. J. (2008). High impulsivity predicts the switch to compulsive cocaine-taking. Science, 320, 1352–1355.
Belzung, C., Misslin, R., Vogel, E., Dodd, R. H., & Chapouthier, G. (1987). Anxiogenic effects of methyl-beta-carboline-3-carboxylate in a light/dark choice situation. Pharmacology, Biochemistry, and Behavior, 28, 29–33.
Blanchard, D. C., Hynd, A. L., Minke, K. A., Minemoto, T., & Blanchard, R. J. (2001a). Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals. Neuroscience and Biobehavioral Reviews, 25, 761–770.
Blanchard, D. C., Griebel, G., & Blanchard, R. J. (2001b). Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic. Neuroscience and Biobehavioral Reviews, 25, 205–218.
Blier, P., Pineyro, G., el Mansari, M., Bergeron, R., & de Montigny, C. (1998). Role of somatodendritic 5-HT autoreceptors in modulating 5-HT neurotransmission. Annals of the New York Academy of Sciences, 861, 204–216.
Bloom, F. E. & Kupfer, D. J., eds. (1995). Psychopharmacology: the Fourth Generation of Progress. New York, NY: Raven Press.
Bodnoff, S. R., Suranyi-Cadotte, B., Quirion, R., & Meaney, M. J. (1989). A comparison of the effects of diazepam versus several typical and atypical anti-depressant drugs in an animal model of anxiety. Psychopharmacology (Berlin), 97, 277–279.
Borsini, F., Podhorna, J., & Marazziti, D. (2002). Do animal models of anxiety predict anxiolytic-like effects of antidepressants?Psychopharmacology (Berlin), 163, 121–141.
Drevets, W. C., Thase, M. E., Moses-Kolko, E. L., et al. (2007). Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nuclear Medicine and Biology, 34, 865–877.
Drugan, R. C., Ryan, S. M., Minor, T. R., & Maier, S. F. (1984). Librium prevents the analgesia and shuttlebox escape deficit typically observed following inescapable shock. Pharmacology Biochemistry and Behavior, 21, 749–754.
Dulawa, S. C., & Hen, R. (2005). Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test. Neuroscience and Biobehavioral Reviews, 29, 771–783.
Fava, M., Rush, A. J., Alpert, J. E., et al. (2008). Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. American Journal of Psychiatry, 165, 342–351.
File, S. E. (1980). The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. Journal of Neuroscience Methods, 2, 219–238.
Frazer, A., & Morilak, D. A. (2005). What should animal models of depression model?Neuroscience and Biobehavioral Reviews, 29, 515–523.
Gambarana, C., Scheggi, S., Tagliamonte, A., Tolu, P., & De Montis, M. G. (2001). Animal models for the study of antidepressant activity. Brain Research. Brain Research Protocols, 7, 11–20.
Gardier, A. M., Malagie, I., Trillat, A. C., Jacquot, C., & Artigas, F. (1996). Role of 5-HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies. Fundamental and Clinical Pharmacology, 10, 16–27.
Gordon, J. W., Scangos, G. A., Plotkin, D. J., Barbosa, J. A., & Ruddle, F. H. (1980). Genetic transformation of mouse embryos by microinjection of purified DNA. Proceedingss of the National Academy of Sciences of the USA, 77, 7380–7384.
Gossen, M., & Bujard, H. (1992). Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proceedings of the National Academy of Sciences of the USA, 89, 5547–5551.
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry, 160, 636–645.
Gross, C., Zhuang, X., Stark, K., et al. (2002). Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature, 416, 396–400.
Haller, J., Halasz, J., & Majercsik, E. (2004). Psychosocial conditions and the efficacy of clinically available anxiolytics. Current Drug Targets, 5, 655–664.
Heisler, L. K., Chu, H. M., Brennan, T. J., et al. (1998). Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proceedings of the National Academy of Sciences of the USA, 95, 15049–15054.
Hickman-Davis, J. M., & Davis, I. C. (2006). Transgenic mice. Paediatric Respiratory Reviews, 7, 49–53.
Jacob, H. J., & Kwitek, A. E. (2002). Rat genetics: attaching physiology and pharmacology to the genome. Nature Reviews Genetics, 3, 33–42.
Kalueff, A. V., & Murphy, D. L. (2007). The importance of cognitive phenotypes in experimental modeling of animal anxiety and depression. Neural Plasticity, 2007, 52087.
Klemenhagen, K. C., Gordon, J. A., David, D. J., Hen, R., & Gross, C. T. (2006). Increased fear response to contextual cues in mice lacking the 5-HT1A receptor. Neuropsychopharmacology, 31, 101–111.
Koponen, E., Voikar, V., Riekki, R., et al. (2004). Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB-PLCgamma pathway, reduced anxiety, and facilitated learning. Molecular and Cellular Neuroscience, 26, 166–181.
Lapiz-Bluhm, M. D., Bondi, C. O., Doyen, J., et al. (2008). Behavioural assays to model cognitive and affective dimensions of depression and anxiety in rats. Journal of Neuroendocrinology, 20, 1115–1137.
Le Francois, B., Czesak, M., Steubl, D., & Albert, P. R. (2008). Transcriptional regulation at a HTR1A polymorphism associated with mental illness. Neuropharmacology, 55, 977–85.
Leonardo, E. D., & Hen, R. (2008). Anxiety as a developmental disorder. Neuropsychopharmacology, 33, 134–140.
Lister, R. G. (1987). The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berlin), 92, 180–185.
Lo Iacono, L., & Gross, C. (2008). Alpha-Ca2+/calmodulin-dependent protein kinase II contributes to the developmental programming of anxiety in serotonin receptor 1A knock-out mice. Journal of Neuroscience, 28, 6250–6257.
Lucki, I. (1997). The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behavioural Pharmacology, 8, 523–532.
Maren, S. (2001). Neurobiology of Pavlovian fear conditioning. Annual Review of Neuroscience, 24, 897–931.
McKinney, W. T. (1984). Animal models of depression: an overview. Psychiatric Development, 2, 77–96.
Melton, D. W. (1994). Gene targeting in the mouse. Bioessays, 16, 633–638.
Millan, M. J. (2003). The neurobiology and control of anxious states. Progress in Neurobiology, 70, 83–244.
Moret, C., & Briley, M. (2000). The possible role of 5-HT(1B/D) receptors in psychiatric disorders and their potential as a target for therapy. European Journal of Pharmacology, 404, 1–12.
Nemeroff, C. B. (2002). Comorbidity of mood and anxiety disorders: the rule, not the exception?American Journal of Psychiatry, 159, 3–4.
Nemeroff, C. B. (2003). Anxiolytics: past, present, and future agents. Journal of Clinical Psychiatry, 64 (Suppl. 3), 3–6.
Nesse, R. M. (1999). Proximate and evolutionary studies of anxiety, stress and depression: synergy at the interface. Neuroscience and Biobehavioral Reviews, 23, 895–903.
Ohl, F., Toschi, N., Wigger, A., Henniger, M. S., & Landgraf, R. (2001). Dimensions of emotionality in a rat model of innate anxiety. Behavioral Neuroscience, 115, 429–436.
Parks, C. L., Robinson, P. S., Sibille, E., Shenk, T., & Toth, M. (1998). Increased anxiety of mice lacking the serotonin1A receptor. Proceedings of the National Academy of Sciences of the USA, 95, 10734–10739.
Perry, J. L., & Carroll, M. E. (2008). The role of impulsive behavior in drug abuse. Psychopharmacology (Berlin), 200, 1–26.
Porter, R., Bock, G., Clark, S., & Ciba Foundation (1986). Antidepressants and Receptor Function. Chichester; New York, NY: Wiley.
Ramboz, S., Oosting, R., Amara, D. A., et al. (1998). Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proceedings of the National Academy of Sciences of the USA, 95, 14476–14481.
Ressler, K. J., & Nemeroff, C. B. (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and Anxiety, 12 (Suppl. 1), 2–19.
Robbins, T. W. (2002). The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berlin), 163, 362–380.
Rodgers, R. J. (1997). Animal models of “anxiety”: where next?Behavioural Pharmacology, 8, 477–496; discussion 497–504.
Santarelli, L., Saxe, M., Gross, C., et al. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science, 301, 805–809.
Serretti, A., Calati, R., Mandelli, L., & De Ronchi, D. (2006). Serotonin transporter gene variants and behavior: a comprehensive review. Current Drug Targets, 7, 1659–1669.
Sramek, J. J., Zarotsky, V., & Cutler, N. R. (2002). Generalised anxiety disorder: treatment options. Drugs, 62, 1635–1648.
Stark, K. L., Gross, C., Richardson-Jones, J., Zhuang, X., & Hen, R. (2007). A novel conditional knockout strategy applied to serotonin receptors. Handbook of Experimental Pharmacology, 178, 347–363.
van der Staay, F. J. (2006). Animal models of behavioral dysfunctions: basic concepts and classifications, and an evaluation strategy. Brain Research Reviews, 52, 131–159.
Weiss, J. M., Goodman, P. A., Losito, B. G., et al. (1981). Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain. Brain Research Reviews, 3, 167–205.
Willner, P. (1997). Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berlin), 134, 319–329.
Willner, P., & Mitchell, P. J. (2002). The validity of animal models of predisposition to depression. Behavioural Pharmacology, 13, 169–188.
Zohar, J., Kennedy, J. L., Hollander, E., & Koran, L. M. (2004). Serotonin-1D hypothesis of obsessive–compulsive disorder: an update. Journal of Clinical Psychiatry, 65 (Suppl. 14), 18–21.