Brain output dysregulation induced by olfactory bulbectomy: an approximation in the rat of major depressive disorder in humans?

Mounting evidence indicates that the emotional, cognitive, neurovegetative and behavioral symptoms of patients with major depressive disorder are due to abnormal neurochemical substrates in the brain. Although the specific neurochemical abnormalities responsible have not been identified, the presenting symptoms of major depression are consistent with a disruption of normal neural communications between the limbic system and hypothalamus. Following removal of the olfactory bulbs, rats display a syndrome of behavioral deficits that also reflect a disruption of the limbic-hypothalamic axis. Moreover, the bulbectomy induced deficits are selectively reduced by the chronic administration of the same drugs that alleviate the symptoms of depression when given chronically to the patients. In addition to this pharmacological similarity, there are also numerous behavioral parallels between bulbectomized rats and major depression patients. The bulbectomized rat provides a good model in which to study antidepressant drugs and also may provide neurochemical and neuroanatomical data that are relevant to understanding the biological substrates of emotion and the causes of depression in humans.