Dysfunctions of the brain’s serotonin system are thought to underlie the symptoms of depression, primarily because antidepressants that target the serotonin transporters show some clinical success. However, antidepressant efficacy is variable, often delayed and temporary. Because the roles of serotonin in the brain during health and disease are ill-defined, it is extremely challenging for drug developers to develop better, more targeted antidepressant therapies. In this work, we develop and apply novel voltammetric tools and couple them with confocal imaging, animal behavior and mathematical models to characterize serotonin neurotransmission in different animal models of depression. Specifically, we find that alterations in another neurotransmitter system, the histamine system, likely modulate abnormalities in the serotonin system. Additionally, we find that rapid changes in serotonin transporter function may be responsible for the dosing and delayed therapeutic issues of common antidepressants. We model the experimental data and offer mechanistic insights into how histamine and serotonin modulate one another in health and disease and this leads us to hypothesize why antidepressants are not universally effective. The data afforded by our chemical tools has the capacity to profoundly improve therapeutic strategies towards depression by shedding light on another important player.

Novel perspectives on psychiatric diseases with microengineered, electrochemical detection platforms

256th National Meeting (2018)

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