Antidepressant drug‐induced stimulation of mouse hippocampal neurogenesis is age‐dependent and altered by early life stress

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Abstract
The continuous generation of new neurons in the adult hippocampus exhibits remarkable plasticity. Decreased neurogenesis is thought to underlie depression‐like behaviors, and increased neurogenesis is thought to occur following antidepressant drug treatment. Studies on different strains of mice, however, yielded contrasting results with regard to the link between behavioral modifications induced by antidepressant drugs or environmental enrichment and changes in adult hippocampal neurogenesis. Therefore, we conducted a comparative study on the inbred strains Balb/c and C57Bl/6 that differ substantially in emotionality, stress reactivity, and behavioral responses to chronic antidepressant drugs. Quantitative assessments of progenitor cell proliferation and immature neuronal differentiation in the dentate gyrus revealed that, despite significantly different basal proliferation rates between both strains, neither strain exhibited changes in adult neurogenesis after exposure to early life stress or adult chronic fluoxetine treatment. A stimulatory effect of fluoxetine on adult hippocampal neurogenesis was only detected when treatment was initiated during adolescence, and this effect was abolished in mice exposed to early life stress, a prominent risk factor for developing adult‐onset depression‐like behaviors. Thus, in both strains of mice neither adult fluoxetine treatment nor adolescent fluoxetine treatment following early life stress exposure increased the proliferation and early differentiation of adult neural progenitor cells. J. Comp. Neurol. 509:372–381, 2008.