Brain dopamine and serotonin differ in regulation and its consequences
Brain dopamine and serotonin differ in regulation and its consequences
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DOI：
10.1073/pnas.1201547109
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发表时间：
2012-07-17
影响因子：
11.1
通讯作者：
Wightman, R. Mark
中科院分区：
文献类型：
--
作者：
Hashemi, Parastoo;Dankoski, Elyse C.;Wightman, R. Mark
多巴胺和血清素（5-羟色胺或5-HT）是与许多心理障碍有关的神经递质。虽然多巴胺在大脑中的传输已被广泛研究，在体内快速扫描循环伏安法，检测5-HT使用体内伏安法最近才建立。在这项工作中，我们使用两个碳纤维微电极，同时测量多巴胺的释放在延髓核和5-HT的释放在黑质网状部，使用一个共同的刺激在一个单一的大鼠。我们发现，5-HT的释放是深刻的限制相比，多巴胺的释放，尽管相当的组织含量水平。利用生理和药理学分析，我们发现，5-HT的传输是最敏感的摄取和代谢降解机制。相反，多巴胺的传递受到合成和重新包装的限制。最后，我们表明，通过同时抑制摄取和代谢降解来破坏β-羟色胺能调节机制可能会产生模拟5-羟色胺综合征的严重生理后果。
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.