Monitoring Dopamine Responses to Potassium Ion and Nomifensine by in Vivo Microdialysis with Online Liquid Chromatography at One-Minute Resolution.
Monitoring Dopamine Responses to Potassium Ion and Nomifensine by in Vivo Microdialysis with Online Liquid Chromatography at One-Minute Resolution.
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DOI：
10.1021/acschemneuro.6b00383
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发表时间：
2017-02-15
影响因子：
5
通讯作者：
Weber SG
中科院分区：
文献类型：
--
作者：
Ngo KT;Varner EL;Michael AC;Weber SG
最近，我们的实验室已经证明了技术的可行性，监测多巴胺在一分钟的时间分辨率与微透析和在线液相色谱。在这里，我们监测多巴胺在大鼠纹状体局部交付高钾/低钠或诺米芬辛清醒行为大鼠。植入微透析探针，并在灌注液中加入或不加入地塞米松连续灌注4天。地塞米松是一种抗炎剂，对微透析探针周围脑组织的表观健康表现出几种积极作用。在基础条件下植入后1天或4天，在60 mM或100 mM K+的10分钟应用期间，以及在10 μM诺米芬辛的15分钟应用期间，监测多巴胺。通过使用计算机控制的低死体积六端口阀将高K +或诺米芬辛添加到微透析灌注液中来局部递送高K +或诺米芬辛。每天/K+/地塞米松组合引起特异性多巴胺反应。地塞米松治疗增加了基础透析液中的多巴胺水平（即，在不存在K+或诺米芬新的情况下）。60 mM K+的应用程序引起不同的反应，在第一天和第四天后的探针植入，这取决于地塞米松的存在或不存在，与地塞米松的能力，以减轻探针植入的创伤性影响。应用100 mM K+诱发多巴胺水平的剧烈振荡，与微透析探针附近植入的金属电极处的场电位变化相关。这一结果的组合表明了响应于100 mM K+的扩展去极化的作用。与一分钟的时间分辨率，我们发现，它是可能的，以表征的药代动力学的反应，局部递送诺米芬新。总体而言，本文报告的研究结果证实了通过微透析以高灵敏度和高时间分辨率监测多巴胺的能力所带来的益处。
Recently, our laboratory has demonstrated the technical feasibility of monitoring dopamine at one-min temporal resolution with microdialysis and online liquid chromatography. Here, we monitor dopamine in the rat striatum during local delivery of high potassium/low sodium or nomifensine in awake-behaving rats. Microdialysis probes were implanted and perfused continuously with or without dexamethasone in the perfusion fluid for four days. Dexamethasone is an anti-inflammatory agent that exhibits several positive effects on the apparent health of the brain tissue surrounding microdialysis probes. Dopamine was monitored one or four days after implantation under basal conditions, during 10-min applications of 60 mM or 100 mM K+, and during 15-min applications of 10 μM nomifensine. High K + or nomifensine were delivered locally by adding them to the microdialysis perfusion fluid using a computer-controlled, low-dead-volume six-port valve. Each day/K+/dexamethasone combination elicited specific dopamine responses. Dexamethasone treatment increased dopamine levels in basal dialysates (i.e., in the absence of K+ or nomifensine). Applications of 60 mM K+ evoked distinct responses on days one and four after probe implantation, depending upon the presence or absence of dexamethasone, consistent with dexamethasone’s ability to mitigate the traumatic effect of probe implantation. Applications of 100 mM K+ evoked dramatic oscillations in dopamine levels that correlated with changes in the field potential at a metal electrode implanted adjacent to the microdialysis probe. This combination of results indicates the role of spreading depolarization in response to 100 mM K+. With one-min temporal resolution we find that it is possible to characterize the pharmacokinetics of the response to the local delivery of nomifensine. Overall, the findings reported here confirm the benefits arising from the ability to monitor dopamine via microdialysis at high sensitivity and at high temporal resolution.