Animal models of depression: parallels and correlates to severe depression in humans.

Drugs with antidepressant properties in patients with severe depression also have various behavioral and neurochemical effects in animals. This has given rise to numerous animal models that have been suggested to be valid for research into the neurobiology of depression and the neurochemical mechanisms of the antidepressant drugs. However, considerable evidence from many avenues of research indicates that severe depression is a biochemical disorder that develops in those individuals with some predisposing neurochemical vulnerability. Although the predisposing biochemical abnormality has not been identified, it may be related to the neurochemical mechanisms that regulate impulse traffic in various neural systems and maintain the homeostatic balance of neural activity within the brain. Therefore, the appropriate animal model for severe depression should have some disruption of neural functioning that is returned to normal by the chronic administration of antidepressant drugs. Of the numerous animal models of depression that have been presented in the literature, only the rat with olfactory bulb lesions meets this requirement. The behavioral and endocrine abnormalities induced by the olfactory bulb lesions are reversed by chronic (but not acute) treatment with antidepressants of various classes. Of the existing animal models of severe depression, the olfactory bulbectomy model holds the most promise for elucidating the neurobiology of depression and the neurochemistry of antidepressant drugs.