Chronic Treatment with Imipramine and Lithium Increases Cell Proliferation in the Hippocampus in Adrenocorticotropic Hormone-Treated Rats

Adult hippocampal neurogenesis is reported to change in animal models of depression and antidepressants. We have used the mitotic marker 5-bromo-2'-deoxyyridine to address the effects of imipramine and lithium on cell proliferation and survival following chronic treatment with adrenocorticotropic hormone (ACTH) in the subgranular zone of the hippocampal dentate gyros. ACTH treatment for 14d decreased adult hippocampal cell proliferation and survival. Coadministration of imipramine and lithium for 14d blocked the loss of cell proliferation but not cell survival resulting from the chronic treatment with ACTH. The coadministration of imipramine and lithium may have treatment-resistant antidepressive properties, which may be attributed, in part, to a normalization of hippocampal cell proliferation. Major depressive disorder is a debilitating potentially fatal illness with greater than 15% lifetime prevalence in the U.S. population1). Depression currently ranks among the top ten causes of disability among the world's population2). Psychoendocrinological studies have focused on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in patients with depression3,4).