Animal models anxiety disorders

There are three generally accepted criteria for validating animal models for human psychiatric disorders face validity, construct validity, and predictive validity. Face validity refers to the outward appearance of the model, i.e. does the animal s behavior adequately reflect the human behavior being modeled In this dimension, anxiety models have a clear advantage over other psychiatric models it is usually quite apparent if an animal is frightened, whereas it is a much more difficult to assess whether an animal is displaying psychotic-like or depressive-like behavior, for example. 

These examples underline that in the search for animal models of anxiety disorders it is not sufficient to screen for anxiety-related behavioral characteristics. On the contrary, it is of fundamental importance to phenotype extensively and carefully each potential animal model, even the well-established inbred mouse strains. 

Liebsch G, Linthorst ACE, Neumann ID, Reul JMHM, Holsboer F, Landgraf R (1998) Behavioral, physiological, and neuroendocrine stress responses and differential sensitivity to diazepam in two Wistar rat lines selectively bred for high and low anxiety-related behavior. Neuropsychopharmacology 19 381-396 Lister RG (1990) Ethologically based animal models of anxiety disorders. Pharmacol Ther 46 321-340... 

Griebel G (1995) 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders more than 30 years of research. Pharmacol Ther 65 319-395 Griebel G, Belzung C, Perrault G, Sanger DJ (2000) Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice. Psychopharmacology (Berl) 148 164-170... 

Ramboz S, Oosting R, Amara DA, Kung HP, Blier P, Mendelsohn M, Mann JJ, Brunner D, Hen R (1998) Serotonin receptor lA knockout an animal model of anxiety-related disorder. ProcNatl Acad Sci U S A 95 14476-14481... 

Stress is thought to be an important factor in the pathophysiology of depression and anxiety disorders. It seems possible that the reduced stress reactivity of NKl receptor- and tael-deficient mice has contributed to the behavioral phenotypes observed in the animal models of anxiety and depression. 

Many patients with anxiety disorders experience an increased susceptibihty to psychosocial stress. Behavioral sensitization may account for these cHnical phenomena, hi the laboratory model of sensitization, single or repeated exposure to physical stimuU or pharmacological agents sensitizes an animal to subsequent stressors (reviewed in Charney et al. 1993). For example, in animals with a history of prior stress, there is a potentiated release of NE in the hippocampus with subsequent exposure to stressors (Nisenbaum et al. 1991). Similar findings were observed in medial prefrontal cortex (Finlay and Abercrombie 1991). The hypothesis that sensitization is underlying neural mechanism contributing to the course of anxiety disorders is supported by clinical studies demonstrating that repeated exposure to traumatic stress is an important risk factor for the development of anxiety disorders, particularly PTSD (Table 1). 

---