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Striatal Crosstalk Between Dopamine and Serotonin Systems

Liu, Y.; Traba, J. E.; Luscher, C.

2025-05-26 neuroscience
10.1101/2025.03.28.645922 bioRxiv
Show abstract

Dopamine (DA) and serotonin (5-HT) are neuromodulators in reward processing, decision- making, and motivated behavior. While often viewed as opposing or complementary systems, how DA and 5-HT release integrate in the striatum remains elusive. Using optogenetics, fiber photometry, and slice electrophysiology, we found that ventral tegmental area (VTA) DA neuron stimulation increased DA release without affecting 5-HT release. Dorsal raphe nucleus (DRN) 5-HT neuron activation, on the other hand, induced serotonin release and a transient increase in DA in the NAc, likely via glutamate co-release onto VTA DA neurons during the initial stimulation phase. These findings indicate that DA and 5-HT operate largely independently in the striatum, with selective circuit-dependent interactions. This work refines our understanding of DA-5HT interactions and provides a foundation for future research into their roles in motivated behaviors and neuropsychiatric disorders.

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