The modulation of paroxetine to the suppressive effect of corticosteroid on adult hippocampal neurogenesis

Abstract

Background: Clinical experience and previous research showed that cognitive deficiency or emotional changes might occur with chronic treatment of glucocorticoids. Results from animal studies, suggested that this might be caused by the suppressive effect of glucocorticoid on hippocampal neurogenesis. Paroxetine is a specific and potent serotonin uptake inhibitor antidepressant (SSRI) commonly used in psychiatry. Here, we investigated whether the long term use of Paroxetine 1) increases adult hippocampal neurogenesis and 2) reverses the reduced neurogenesis induced by corticosteroid. Methods: Adult male SD rats were given daily injection of vehicle, corticosteroid, Paroxetine, or both corticosteroid and Paroxetine for 14 days. Cell proliferation in the dentate gyrus was quantified by using BrdU immunohistochemistry, and the number of BrdU positive cells was evaluated. Results: Our results showed that corticosteroids suppressed hippocampal neurogenesis. Chronic Paroxetine treatment alone resulted in the increase of adult hippocampal neurogenesis. More importantly, this treatment could reverse the suppressive effect of corticosteroid on hippocampal neurogenesis. Conclusion: These data demonstrate that chronic treatment with paroxetine can protect the hippocampus from the potentially deleterious effects of corticosteroid on neurogenesis which provides a clue to prevent hippocampal damage during the chronic use of glucocorticoids in the clinic. Corresponding authors: KF So and SW Tang.