Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

TLDR

Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. The study investigates whether disrupting antidepressant‑induced neurogenesis abolishes behavioral responses to antidepressants. Genetic and radiological methods were used to selectively inhibit hippocampal neurogenesis. Serotonin 1A receptor null mice were insensitive to fluoxetine’s neurogenic and behavioral effects, X‑irradiation of the hippocampus blocked the neurogenic and behavioral effects of two antidepressant classes, and these results indicate that chronic antidepressants’ behavioral effects are mediated by hippocampal neurogenesis.

Abstract

Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.