Striatal dopamine and serotonin release operate largely in parallel with limited, asymmetric crosstalk

Abstract

Dopamine and serotonin jointly regulate striatal functions that support reinforcement, decision-making and motivated behavior, yet whether activity in one system directly recruits release from the other remains unclear. Using anatomical tracing, cell type-specific optogenetics and genetically encoded fluorescent sensors, we measured dopamine and serotonin dynamics in the nucleus accumbens and dorsal striatum after cocaine administration and selective neuronal stimulation. Activation of ventral tegmental area dopamine neurons increased dopamine release without affecting serotonin. In contrast, activation of dorsal raphe serotonergic neurons robustly increased serotonin and weakly entrained dopamine signals without producing a sustained increase in dopamine amplitude. These findings indicate that striatal dopamine and serotonin release operate largely in parallel, with limited and directionally asymmetric crosstalk.