RT Journal Article SR Electronic T1 Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9104 OP 9110 DO 10.1523/JNEUROSCI.20-24-09104.2000 VO 20 IS 24 A1 Jessica E. Malberg A1 Amelia J. Eisch A1 Eric J. Nestler A1 Ronald S. Duman YR 2000 UL http://www.jneurosci.org/content/20/24/9104.abstract AB Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.