Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11510-5. doi: 10.1073/pnas.1201547109. Epub 2012 Jul 9.
Dopamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters that are implicated in many psychological disorders. Although dopamine transmission in the brain has been studied extensively in vivo with fast scan cyclic voltammetry, detection of 5-HT using in vivo voltammetric methods has only recently been established. In this work we use two carbon-fiber microelectrodes to simultaneously measure dopamine release in the nucleus accumbens and 5-HT release in the substantia nigra pars reticulata, using a common stimulation in a single rat. We find that 5-HT release is profoundly restricted in comparison with dopamine release despite comparable tissue content levels. Using physiological and pharmacological analysis, we find that 5-HT transmission is mostly sensitive to uptake and metabolic degradation mechanisms. In contrast, dopamine transmission is constrained by synthesis and repackaging. Finally, we show that disruption of serotonergic regulatory mechanisms by simultaneous inhibition of uptake and metabolic degradation can have severe physiological consequences that mimic serotonin syndrome.
多巴胺和 5-羟色胺（5-羟色胺或 5-HT）是与许多心理障碍有关的神经递质。虽然已经使用快速扫描循环伏安法在体内对大脑中的多巴胺传递进行了广泛的研究，但使用体内伏安法检测 5-HT 最近才得以建立。在这项工作中，我们使用两根碳纤维微电极在单个大鼠中使用共同刺激，同时测量伏隔核中的多巴胺释放和黑质网状部中的 5-HT 释放。我们发现，尽管组织含量水平相当，但与多巴胺释放相比，5-HT 释放受到严重限制。通过生理和药理学分析，我们发现 5-HT 传递主要对摄取和代谢降解机制敏感。相比之下，多巴胺传递受到合成和重新包装的限制。最后，我们表明，同时抑制摄取和代谢降解可以破坏 5-羟色胺调节机制，从而产生类似于 5-羟色胺综合征的严重生理后果。
