Development of valid animal models for human affective disorder. Attempts have involved numerous approaches such as the exploitation of vulnerability factors for depression including maternal deprivation, exposure to psychophysiological stress or by pharmacological depletion of monoamines. However, no approach is perhaps so radical as the removal of a part of the brain as occurs in the olfactory bulbectomy (OB) model of depression. The ensuing behavioural symptoms also distinguish the OB model from other animal models of depression, in that it possesses significant face validity as a model of agitated depression. OB in rodents provokes behavioural changes that respond to chronic but not acute treatment with antidepressants thus mimicking the time-course of antidepressant action in the clinic. The persistent use and popularity of the model over the past 25 years is a testament to its utility in exploring the neurobiological mechanisms of antidepressant action, as well as the pathophysiology of major depression. In this review, the present status of the model is presented. (C) 2003 Elsevier B.V. All rights reserved.