Partial serotonergic denervation decreases progenitor cell proliferation in the adult rat hippocampus, but has no effect on rat behavior in the forced swimming test

Abstract

It has been hypothesized that impaired serotonin (5-HT) neurotransmission contributes to the pathophysiology of depression. Recently, it was shown in adult animals that antidepressants which influence 5-HT levels increase hippocampal progenitor cell proliferation, suggesting an important role of the 5-HT system in the regulation of adult neurogenesis. In this study, we investigated the effects of partial 5-HT denervation of the adult rat forebrain caused by a single para-chloroamphetamine (PCA) administration (10 mg/kg, s.c.) on hippocampal progenitor cell proliferation measured by Ki-67 immunohistochemistry over a 3-week time period. Moreover, behavior of rats was analyzed by using the forced swimming test which serves as a so-called animal model of depression. One week after PCA administration, a significant decrease of Ki-67 immunopositive cells and cell clusters (−25% and −53%, respectively) was found which was recovered over the 3-week period. The decrease in progenitor cell proliferation in the dentate gyrus per animal was positively correlated with the 5-HT denervation. Behavioral analysis of rats revealed no significant differences between vehicle and PCA-treated animals at any of the examined time points. These findings indicate a regulative role of 5-HT for hippocampal progenitor cell proliferation and neurogenesis, but its relation to animal models of depression remains to be elucidated.