The involvement of dentate gyrus (DG) neurogenesis in the antidepressant action of selective serotonin reuptake inhibitors (SSRIs) is not known. The effects of the SSRI fluoxetine on the hypothalamic–pituitary–adrenal axis and on anxiety-like behaviours were reduced in mice following deletion of serotonin 1A receptor (5-HT1AR) from mature DG granule cells (DGGCs), but not in mice lacking 5-HT1AR selectively in new, adult-born DGGCs. Conversely, selective expression of 5-HT1ARs exclusively in DGGCs resulted in normal behavioural, neuroendocrine and neurogenic responses to fluoxetine, suggesting that DGGCs expressing 5-HT1AR are sufficient to mediate the effects of this drug.
References
Samuels, B. A. et al. 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nat. Neurosci. http://dx.doi.org/10.1038/nn.4116 (2015)
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Lewis, S. Old and young. Nat Rev Neurosci 16, 646 (2015). https://doi.org/10.1038/nrn4047
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DOI: https://doi.org/10.1038/nrn4047
