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Recent Progress in Opioid Research from an Electrophysiological Perspective.
Molecular Pharmacology ( IF 3.6 ) Pub Date : 2020-10-01 , DOI: 10.1124/mol.119.119040
William T Birdsong 1 , John T Williams 2
Affiliation  

Electrophysiological approaches provide powerful tools to further our understanding of how different opioids affect signaling through opioid receptors; how opioid receptors modulate circuitry involved in processes such as pain, respiration, addiction, and feeding; and how receptor signaling and circuits are altered by physiologic challenges, such as injury, stress, and chronic opioid treatment. The use of genetic manipulations to alter or remove μ-opioid receptors (MORs) with anatomic and cell type specificity and the ability to activate or inhibit specific circuits through opto- or chemogenetic approaches are being used in combination with electrophysiological, pharmacological, and systems-level physiology experiments to expand our understanding of the beneficial and maladaptive roles of opioids and opioid receptor signaling. New approaches for studying endogenous opioid peptide signaling and release and the dynamics of these systems in response to chronic opioid use, pain, and stress will add another layer to our understanding of the intricacies of opioid modulation of brain circuits. This understanding may lead to new targets or approaches for drug development or treatment regimens that may affect both acute and long-term effects of manipulating the activity of circuits involved in opioid-mediated physiology and behaviors. This review will discuss recent advancements in our understanding of the role of phosphorylation in regulating MOR signaling, as well as our understanding of circuits and signaling pathways mediating physiologic behaviors such as respiratory control, and discuss how electrophysiological tools combined with new technologies have and will continue to advance the field of opioid research.

中文翻译:

从电生理角度看阿片类药物研究的最新进展。

电生理学方法为进一步了解不同的阿片类药物如何影响阿片受体的信号传导提供了有力的工具。阿片受体如何调节与疼痛,呼吸,成瘾和进食等过程有关的电路;以及生理性挑战(例如损伤,压力和慢性阿片类药物治疗)如何改变受体信号传导和回路。使用遗传操作来改变或去除μ具有解剖学和细胞类型特异性,并具有通过光或化学发生方法激活或抑制特定电路的能力的类阿片受体(MOR)与电生理,药理学和系统级生理学实验结合使用,以扩大我们对有益物质的了解和阿片类药物和阿片受体信号传导的不良适应作用。研究内源性阿片肽信号传导和释放以及响应于长期使用阿片类药物,疼痛和压力的这些系统动力学的新方法,将使我们对脑回路中阿片类药物调制的复杂性有了新的认识。这种理解可能会导致药物开发或治疗方案的新目标或新方法,从而可能影响操纵与阿片类药物介导的生理和行为有关的回路活动的急性和长期效果。这篇综述将讨论我们对磷酸化在调控MOR信号传导中的作用的理解以及对介导诸如呼吸控制等生理行为的电路和信号传导途径的理解的最新进展,并讨论与新技术结合的电生理工具如何并将继续促进阿片样物质研究领域。
更新日期:2020-09-21
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