One of the two core symptom of human depression is anhedonia, the loss of interest of pleasure in daily activities. Daily stressful life events are recognized as predisposing factors in the etiology of depression. Rats submitted to a regimen of chronic, mild, unpredictable stress exhibit behavioral deficits consistent with a loss of responsiveness to reward, such as decreased sucrose consumption, decreased ability to associate rewards with a distinctive environment, and decreased sensitivity to rewarding electrical brain stimulation. Normal behavior can be restored by chronic treatment with tricyclic antidepressants, atypical antidepressants, monoamine oxidase inhibitors and electroshocks, but not by other psychotropic agents such as antipsychotics. In addition, chronically stressed animals exhibit REM sleep abnormalities resembling those observed in depressed patients and recognized as biological makers of depression. These data provide evidence supporting chronic stress-induced anhedonia in rats as a novel animal model of human depression combining convergent elements of biological, etiological, symptomatological and therapeutic validity. This realistic simulation of a core feature of depression may prove useful for a better understanding of pathophysiological mechanisms involved in depressive disorders.