Sci. STKE, 12 April 2005
ANTIDEPRESSANTS Serotonin Takes a Detour
The striatum in the mammalian brain controls cognitive and adaptive behaviors and is innervated by dopamine (DA) and serotonin (5-HT) secreting neurons. The effects of both neurotransmitters are controlled by specific reuptake transporters expressed by each neuron. Under normal conditions, secreted 5-HT is taken up again by serotonin transporters (SERTs), thus keeping the extracellular concentration of the neurotransmitter low. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are effective antidepressants that prolong and elevate extracellular 5-HT concentrations. However, Zhou et al. report that striatal DA transporters (DATs) also reuptake 5-HT into dopamine nerve terminals, thus influencing 5-HT signaling dynamics. Furthermore, 5-HT and DA are subsequently released together from DA neurons, potentially inducing simultaneous 5-HT and DA signaling. Immunostaining and electrochemical measurements of DA and 5-HT release in mouse striatum slices indicated that when treated with exogenous 5-HT, 5-HT entered DA nerve terminals. However, blocking DATs with a drug inhibitor prevented this reuptake. Cyclic voltammetry was also applied to striatal slices to differentially measure DA and 5-HT release evoked by electrical stimulation. Electrochemical measurements suggested action potential-dependent vesicular corelease of both neurotransmitters by DA neurons. The ability of the SSRI fluoxetine to promote corelease of 5-HT and DA from DA neurons was inhibited when DATs were blocked, further suggesting accumulation of 5-HT in DA neurons by DATs. Thus, the effect of antidepressants and the signaling dynamics of 5-HT and DA on behavioral output may be altered by this transport pathway.
F.-M. Zhou, Y. Liang, R. Salas, L. Zhang, M. De Biasi, J. A. Dani, Corelease of dopamine and serotonin from striatal dopamine terminals. Neuron 46, 65-74 (2005). [PubMed]
Citation: Serotonin Takes a Detour. Sci. STKE 2005, tw131 (2005).
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