title: Animal models of depression reflect changing views on the essence and etiology of depressive disorders in humans.
abstract: 1. Since it is ethically unacceptable to use human subjects to conduct manipulative experimental hypothesis-testing research on major depression, investigators interested in the development, the substrates or the mechanisms of treatment of depressive disorders have turned to observational models with humans or to interactive models with animals. 2. One of the earliest animal models of depression, the infant/mother separation in monkeys, is based on the Freudian notion of the loss-inward directed anger-depression connection. 3. The hypothesis that depression is caused by stress led to the development of numerous animal models of depression based on the behavioral abnormalities induced in animals, usually rats but occasionally other species, by exposure to prolonged or intense stress. 4. The selective therapeutic efficacy of antidepressant drugs suggested the hypothesis that depression is caused by a neurochemical abnormality that is alleviated by chronic exposure to antidepressants. This hypothesis has been refined to state that depressive disorders are caused by genetically based neurochemical dysregulation of neural activity in the limbic system. 5. Models based on the limbic dysfunction hypothesis could be used to explore the specific neural substrates of depression. At present, the rat with limbic dysfunction induced by olfactory bulbectomy appears to fulfill best the requirements for a model of depression. The future development or discovery of a genetic strain of animals that shows comparable behavioral and neurovegetative deficits and similar selective drug responses to those seen in patients with depressive disorder, would make tremendous contributions to the understanding not only of depression but also of the neurobiology of the limbic system.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Richardson
mesh_terms: D000818:Animals; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D004195:Disease Models, Animal; D006801:Humans