The serotonergic system is a high-centrality node in the brain network implicated in affective disorders and their treatment. We use optogenetics, fMRI, and pharmacology to image serotonergic effects of antidepressant treatment in mice at the whole-brain level. We stimulate the ascending serotonergic system and perform functional imaging at multiple time points over the course of antidepressant (fluoxetine) treatment. We establish the feasibility of this paradigm, and report two trends in serotonergic kinetics: (a) increased serotonergic system signal transmission upon acute, but not chronic fluoxetine administration, (b) decreased serotonergic system excitability during the first phase of chronic fluoxetine administration.
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