Depression models

The brain pathologies that mediate the cognitive, motivational, and motor abnormalities of depressive disorders remain elusive. Similarly, the brain mechanisms that confer individual vulnerability to stress and those that precipitate and sustain clinical depression are poorly understood. One approach to these problems has been to try and model the complex neurobiological and behavioral alterations associated with human depression in laboratory animals. Thus, the term depression model refers to any experimental preparation that facilitates the study of human depression-related phenomena by comparing target behaviors and biological functions across species. Usually this involves the generation of behavioral or physiological changes in laboratory animals following an explicit intervention, such as the application of stress. It should be emphasized that such models of a complex disease state need not actually (and are in fact not likely to) produce the disease in the laboratory animal. It is sufficient that a depression model strive to reproduce one critical aspect of the disease process. Similarly, it is not essential that the phenomenon under study demonstrate a response to antidepressant drug administration (unless this is the purpose of the model) although this is often sought. This overview of depression models first addresses general theoretical considerations concerning the validity of the approach, followed by a review of candidate neural mechanisms through which stress might influence behavioral responses to reward. This is followed by a brief review of stress-based animal models of depression