Chronic Fluoxetine Stimulates Maturation and Synaptic Plasticity of Adult-Born Hippocampal Granule Cells

Abstract

Chronic treatments with selective serotonin reuptake inhibitors (SSRIs) have been shown to increase hippocampal neurogenesis. However, it is not known whether SSRIs impact the maturation and functional integration of newborn neurons. Here we examined the effects of subchronic and chronic fluoxetine on the structural and physiological properties of young granule cells. Our results show that doublecortin-positive immature neurons displayed increased dendritic arborization after chronic fluoxetine treatment. In addition, chronic but not subchronic fluoxetine elicited a decrease in the number of newborn neurons expressing immature markers and a corresponding increase in those expressing mature markers. These results suggest that chronic fluoxetine accelerates the maturation of immature neurons. We also investigated the effects of fluoxetine on a form of neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus. This form of LTP was enhanced by chronic fluoxetine, and ablation of neurogenesis with x-irradiation completely blocked the effects of chronic fluoxetine on LTP. Finally, we demonstrated that the behavioral effect of fluoxetine in the noveltysuppressed feeding test requires chronic administration and is blocked by x-irradiation. These results show that the effects of fluoxetine on LTP and behavior both require neurogenesis and follow a similar delayed time course. The effects of chronic fluoxetine on the maturation and functional properties of young neurons may therefore be necessary for its anxiolytic/antidepressant activity and contribute to its delayed onset of therapeutic efficacy.

Rapid Anxiolytic Effects of a 5-HT4 Receptor Agonist Are Mediated by a Neurogenesis-Independent Mechanism

“…We have seen these effects of repeated testing routinely. For example, in the NSF paradigm, the latency to feed was decreased after a second exposure to the test (Wang et al, 2008). In the present study, we observed a decrease in the time spent in the center of the arena owing to the re-exposure to the test in all treated groups.…”

Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus

“…A recent study showed that fluoxetine, known to enhance the proliferation of early progenitors cells in the adult brain (Encinas et al, 2006), also increases the maturation and survival of newborn neurons at 21 days post-BrdU (Wang et al, 2008). Here, we found that agomelatine appeared to induce an early acceleration of cell maturation at 8 days of development.…”

Heat-Induced Antigen Retrieval: An Effective Method to Detect and Identify Progenitor Cell Types during Adult Hippocampal Neurogenesis

“…Over the past decade, the field of adult hippocampal neurogenesis has seen significant work. The region has attracted much interest since newborn neurons in the SGZ contribute to enhanced neural plasticity that can sustain specific brain functions [1][2][3][4][5] . Adult hippocampal neurogenesis has been implicated to play important roles in mood regulation, regeneration, and learning and memory.…”