Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of thi s study was to investigate the effect of antidepressants on hippocampal neu rogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (B rdU) as a marker for dividing cells. Our studies demonstrate that chronic a ntidepressant 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, ag ents was found to increase BrdU-labeled cell number, indicating that this i s a common and selective action of antidepressants. In addition, upregulati on of the number of BrdU-labeled cells is observed after chronic, but not a cute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant tr eatment 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 possibil ity 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 therapeut ic actions of antidepressant treatment.