Selective serotonin reuptake inhibitors (SSRIs) are commonly used antidepressants; however, their mechanism of action is elusive. The authors here show that activation of serotonin 5-HT1B receptors on cholecystokinin-expressing interneurons (CCK neurons) in the dentate gyrus underlies the effects of acute SSRI treatment on depressive-like behaviours in mice, whereas 5-HT2A receptors mediate the effects of chronic SSRI treatment. Chemogenetic inhibition of CCK neurons had an acute antidepressant effect, suggesting that this neuronal population might be a viable target for the development of improved antidepressants.
References
Medrihan, L. et al. Initiation of behavioral response to antidepressants by cholecystokinin neurons of the dentate gyrus. Neuron http://dx.doi.org/10.1016/j.neuron.2017.06.044 (2017)
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Whalley, K. Acute actions. Nat Rev Neurosci 18, 514 (2017). https://doi.org/10.1038/nrn.2017.106
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DOI: https://doi.org/10.1038/nrn.2017.106