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首页> 外文OA文献 >A FRAMEWORK FOR CHARACTERIZING REGIONAL ALTERATIONS IN DOPAMINE NEUROTRANSMISSION IN THE CONTEXT OF DRUGS AND DISEASE USING FAST-SCAN CYCLIC VOLTAMMETRY
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A FRAMEWORK FOR CHARACTERIZING REGIONAL ALTERATIONS IN DOPAMINE NEUROTRANSMISSION IN THE CONTEXT OF DRUGS AND DISEASE USING FAST-SCAN CYCLIC VOLTAMMETRY

机译：用快速扫描循环伏安法在药物和疾病背景下表征多巴胺神经传递区域变化的框架

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摘要

Dopamine (DA) has become a sort of buzzword as the ‘pleasure’ neurotransmitter that signals for natural rewards, but is ‘hijacked’ by drugs of abuse and the instant gratification we derive from our phones, Facebook, and fast-food diets in the fast-paced world we live in. In reality, DA has much more nuanced and varied functions that include the regulation of attention, working memory, motivation, movement, and even endocrine functions, which largely depends upon the region DA is acting in the brain. Dysfunction of DA neurotransmission is implicated in conditions like Parkinson’s disease (PD), attention deficit/hyperactivity disorder (ADHD), drug addiction, and traumatic brain injury (TBI) to name just a few. As such, the DAergic system represents a rational pharmaceutical target that act as DA receptor agonists, antagonists, indirect agonists, and DA reuptake inhibitors. Understanding how region-specific DA neurotransmission is altered in pathological states and following both acute and chronic drug administration, requires multi-faceted research approaches but can be significantly driven by advancements in research methodologies. It is for this reason that we hope readers will find the work contained herein particularly timely and important. Although the work contained here represents research conducted using fast-scan cyclic voltammetry (FSCV), an electrochemical method to monitor in vivo electrically stimulated DA neurotransmission that has been around since the mid 1980s, we describe the development of a novel quantitative interpretive framework for FSCV data that enhances the ability to characterize the region-specific DA neurotransmission in the context of drugs and diseases. To illustrate the utility of our framework, we demonstrate how our approach has been used to resolve the mechanistic actions of the most commonly used Parkinsonian drug, L-DOPA, on regiospecific DA neurotransmission. Moreover, our framework was utilized to characterize the regiospecific DAergic dysfunction following an experimental model of TBI and the robust neurorestorative effects of chronic methylphenidate treatment in this model. To this end, we not only describe a theoretical framework for characterizing regiospecific alterations in DA neurotransmission, but we also offer practical examples that may serve as a roadmap for studying DA neurotransmission kinetics in the context of drugs and other diseases.
机译：多巴胺（DA）已成为一种流行语，它是发出“自然”回报的“愉悦”神经递质，但由于滥用药物和我们从手机，Facebook和快餐中获取的即时满足而“劫持”我们生活在一个快节奏的世界中。实际上，DA具有细微差别和多种功能，包括注意力，工作记忆，动力，运动乃至内分泌功能的调节，这在很大程度上取决于DA在大脑中的作用区域。 DA神经传递功能障碍与帕金森氏病（PD），注意力不足/多动症（ADHD），药物成瘾和脑外伤（TBI）等疾病有关。因此，DAergic系统代表了一种合理的药物靶标，可充当DA受体激动剂，拮抗剂，间接激动剂和DA再摄取抑制剂。要了解在病理状态下以及急性和慢性药物管理后特定区域的DA神经传递是如何变化的，需要多方面的研究方法，但研究方法的进步可能会极大地推动研究。出于这个原因，我们希望读者能发现本文中的工作特别及时和重要。尽管此处包含的工作代表使用快速扫描循环伏安法（FSCV）进行的研究，该方法是一种监测体内电刺激的DA神经传递的电化学方法，该方法自1980年代中期开始出现，但我们描述了FSCV新型定量解释框架的发展增强在药物和疾病背景下表征区域特异性DA神经传递能力的数据。为了说明我们框架的实用性，我们演示了如何使用我们的方法来解决最常用的帕金森病药物L-DOPA对区域特异性DA神经传递的机械作用。此外，我们的框架被用来表征遵循TBI实验模型的区域特异性DAergic功能障碍以及该模型中慢性哌醋甲酯治疗的强大神经修复​​作用。为此，我们不仅描述了表征DA神经传递中区域特异性改变的理论框架，而且还提供了可作为研究药物和其他疾病背景下DA神经传递动力学的路线图的实际例子。

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    Harun Rashed;

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  • 年度 2015
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