11 Another behavioral approach to simulate a human depressive state in animals is the learned helplessness model. Originally described in dogs subjected to inescapable electric shock,12 this model has received considerable attention in studies of “depression” in mice and rats (for review see refs 13, 14). limitations of the helplessness test as consequence of

foot shock are that the test is difficult to replicate between laboratories15 and that it cannot be routinely used in a number of countries because of ethical or regulator supervision.14 The chronic mild stress model Inhibitors,research,lifescience,medical is based on exposure of animals (usually rats) to uncontrollable stressors. Animals arc subjected, in succession, to a range of mild Tasocitinib mw stressors such as disrupted light-dark cycle, wet bedding, having an intruder rat placed in the home cage, or having the home cage tilted at an angle for 1 to 2 Inhibitors,research,lifescience,medical days.16 The complex procedures

of this model almost ensure that every laboratory will have at least slightly different experimental setups, and consequently, also different interpretations of the protocols.14 Among the most potent factors known to trigger or induce depressive episodes are stressful life events.17-20 Stress is considered to perturb Inhibitors,research,lifescience,medical the homeostasis of an organism in a way that can Inhibitors,research,lifescience,medical lead to a long-lasting imbalance in neurotransmitter, neuroendocrine, and hormonal systems and thus finally to a psychiatric disease. The stress hypothesis of mood disorders has stimulated the development of a number of putative animal models of depression.2-21 Loss of rank and/or social status in humans is one example of loss experiences which are increasingly recognized as specific type of ”life Inhibitors,research,lifescience,medical event“ associated with a great risk of depression.22 A number of behavioral models have sought to stimulate or model depression

by manipulating social relationships in animals, and new powerful animal models using chronic psychosocial Rutecarpine perturbations as stressors have been established (eg, ref 23). In recent years, our group has provided increasing evidence that chronic psychosocial stress in the male tree shrew (Tupaia belangeri) represents a natural and valid paradigm for studying the behavioral, endocrine, and neurobiological changes that may underlie stress-related disorders such as depression.24 Recently, our group has described and validated a new model of chronic social stress in rats25 based on the resident-intruder paradigm originally described by Miczek26 and Koolhaas et al.27 This model, in which depressive -like behavior can be normalized by antidepressants, provides the opportunity to study gene expression in distinct brain areas.