Cell proliferation is decreased in hippocampus of depressed rats and is reversaed by antidepressants

Abstract

The possibility that cellular remodeling may contribute to the pathophysiology of mood disorders has gained ample support based on imaging and morphometric studies. Neurogenesis has been documented in adult brain and plays an important role in neural plasticity and remodeling. There have been some studies indicating decrease in neurogenesis/cell proliferation during stress and that antidepressants increase this process. Very recently we developed an animal model of depression in which repeated stress prolongs the duration of depressive behavior. In this animal model, we reported changes in signaling molecules which were confined to those rats who developed depression and were not related to stress per se. In the present study we tested the hypothesis whether depression is associated with decreased cell proliferation and that antidepressants reverse this decrease. Rats were given inescapable shock on day 1 and day 7, and were tested for escape latency on day 14. Separate groups of depressed rats were given fluoxetine or desipramine for 14 days. A total of 4 BrdU injections, 2 h apart, were given to these rats 24 h before killing. Rats were killed 24 h after the escape test. We observed that cell proliferation was significantly decreased in subgranular zone of depressed rats without any change in subventrivular zone. These changes were significantly reversed by fluoxetine and desipramine treatment, however, the magnitude of reversal was greater with fluoxetine. These changes were significantly correlated with behavioral scores. Our results suggest possible role of neurogenesis in depression and in the mechanism of action of antidepressants.