In the same way that animal models of chronic stress have contributed substantially to an 
understanding of the pathophysiology of coronary artery disease, the direct relation between 
acute stress and cardiac arrhythmias has been shown in dogs (Verrier, 1987). It is 
sympathetically mediated (Rozanski et al., 1999). That acute stress can also cause coronary 
artery endothelial damage has been demonstrated in rats, rabbits, and monkeys; these 
observations may be found to pertain to psychological factors operative during myocardial 
infarction in humans (Rozanski et al., 1999). 
Animal models have played an important role in establishing that psychological stress can 
work together with Helicobacter pylori infection, or through independent pathways, to produce 
peptic ulcer disease (Levenstein et al., 1999). How genetic predisposition may modify the 
ulcerogenic potential of stress has been shown in studies of rat strains that differ as measured 
by emotional reactivity (Redei et al., 1994). Therefore, with increasing knowledge of the rat 
genome, insights at the molecular level into the neurobehavioral mechanisms underlying ulcer 
formation should be forthcoming. Other studies in rats are helping to identify the types of life 
experiences, and presumably associated psychological states, that modulate ulcerogenesis in 
response to a subsequent physical challenge (Overmier and Murison, 2000); these may have 
direct relevance to the design of preventive interventions in humans. 
Animal models incorporating psychosocial distress occupy no less important a role in 
investigations of human mental disorders, as compared with medical disorders. The 
observation that “learned helplessness” could be induced in dogs and other species (Peterson 
et al., 1993; Seligman, 1975) served as one cornerstone of a widely held view that cognitive 
factors operate in precipitating and sustaining human depression (Willner, 1985). While a 
series of clinical studies has demonstrated the important role of psychological stress in the 
pathophysiology of the mood disorders (Kendler et al., 1992; McCauley et al., 1997; Roy, 
1985), experiments in animals subjected to analogous stressors have offered insights into the 
underlying neurophysiological mechanisms. For example, work in rats has shown that 
excessive activity of corticotropin-releasing hormone (CRH) circuitry “may be the persisting 
neurobiological consequence of stress early in development" (Heim et al., 2000). Elevated 
CRHergic function has been implicated in many of the signs and symptoms of human 
depression (Nemeroff et al., 1984). The widespread use of the Porsolt swim test (by which 
immobility is induced in rats placed in a water bath) in screening and identifying anti- 
depressant drugs also attests to the importance of stress induction procedures in animals for 
understanding the mechanisms of human depression and its treatment (Porsolt et al., 1978). 
Fear conditioning in animals involves forming an association between a neutral stimulus, 
discrete or contextual, and an aversive stimulus, generally a foot shock. The physiological 
consequences of fear conditioning strongly resemble human anxiety states (Davis, 1992), and 
a conditioned component to emotional responses has long been recognized in anxiety 
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