Abstract
Dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) fibers broadly innervate the brain. DA transporters (DATs) and 5-HT transporters (SERTs) determine the temporal and spatial extent of the signals, but the transporters are not completely selective. Under circumstances that elevate extracellular 5-HT (such as treatment with antidepressants that block SERTs), DATs expressed on the dense DA terminals of the striatum uptake 5-HT. Subsequently, 5-HT enters DA synaptic vesicles, and DA and 5-HT are co-released. Circumstances also can favor DA loading into 5-HT neurons and terminals. For example, during L-dopa treatment of Parkinson’s disease, 5-HT neurons uptake L-dopa that is subsequently converted to DA, leading to co-release. DA and 5-HT neurons promiscuously uptake each other’s neurotransmitter and co-release occurs under certain conditions. This process induces DA and 5-HT co-signaling mechanisms that have important implications for neuropsychiatric disorders and their treatments.
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Acknowledgments
The authors are supported by grants from the American Parkinson Disease Association, the National Alliance for Research on Schizophrenia and Depression, and the National Institutes of Health (NIDA, NIMH, and NINDS).
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Zhou, FM., Dani, J.A. (2009). Dopamine and Serotonin Crosstalk Within the Dopaminergic and Serotonergic Systems. In: Gutierrez, R. (eds) Co-Existence and Co-Release of Classical Neurotransmitters. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-09622-3_9
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