Department of Chemistry and Biochemistry, University of South Carolina , 631 Sumter Street, Columbia, South Carolina 29208, United States.
Department of Research, Mayo Clinic , Scottsdale, Arizona 85453, United States.
Anal Chem. 2017 Sep 19;89(18):9703-9711. doi: 10.1021/acs.analchem.7b01257. Epub 2017 Sep 7.
The mechanisms that control extracellular serotonin levels in vivo are not well-defined. This shortcoming makes it very challenging to diagnose and treat the many psychiatric disorders in which serotonin is implicated. Fast-scan cyclic voltammetry (FSCV) can measure rapid serotonin release and reuptake events but cannot report critically important ambient serotonin levels. In this Article, we use fast-scan controlled adsorption voltammetry (FSCAV), to measure serotonin's steady-state, extracellular chemistry. We characterize the "Jackson" voltammetric waveform for FSCAV and show highly stable, selective, and sensitive ambient serotonin measurements in vitro. In vivo, we report basal serotonin levels in the CA2 region of the hippocampus as 64.9 ± 2.3 nM (n = 15 mice, weighted average ± standard error). We electrochemically and pharmacologically verify the selectivity of the serotonin signal. Finally, we develop a statistical model that incorporates the uncertainty in in vivo measurements, in addition to electrode variability, to more critically analyze the time course of pharmacological data. Our novel method is a uniquely powerful analysis tool that can provide deeper insights into the mechanisms that control serotonin's extracellular levels.
体内控制细胞外血清素水平的机制尚未明确。这一缺陷使得诊断和治疗涉及血清素的许多精神疾病极具挑战性。快速扫描循环伏安法（FSCV）可测量快速的血清素释放和再摄取事件，但无法报告至关重要的环境血清素水平。在本文中，我们使用快速扫描控制吸附伏安法（FSCAV）来测量血清素的稳态细胞外化学物质。我们对 FSCAV 的“Jackson”伏安波形进行了特征描述，并在体外显示出高度稳定、选择性和灵敏的环境血清素测量。在体内，我们报告海马 CA2 区的基础血清素水平为 64.9 ± 2.3 nM（n = 15 只小鼠，加权平均值 ± 标准误差）。我们通过电化学和药理学验证了血清素信号的选择性。最后，我们开发了一种统计模型，该模型除了电极变异性之外，还纳入了体内测量的不确定性，以更严格地分析药物数据的时间过程。我们的新方法是一种独特的强大分析工具，可以更深入地了解控制血清素细胞外水平的机制。
