Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.
Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.
复制标题
神经类固醇网络对酒精的动态适应。
DOI：
10.1007/164_2017_82
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发表时间：
2018
影响因子：
--
通讯作者：
Jimenez,VanessaA
中科院分区：
文献类型：
--
作者：
Finn,DeborahA;Jimenez,VanessaA
神经类固醇一词是指类固醇激素及其衍生物的快速膜作用，可以通过与配体门控离子通道的相互作用来调节生理功能和行为。本章将重点介绍一组选定的神经类固醇的调节作用的最新进展，这些神经类固醇主要是 γ-氨基丁酸受体 (GABAAR) 的有效正变构调节剂。体内发生的纳摩尔浓度的神经类固醇会增强 GABAAR 介导的抑制的阶段性和强直性形式，表明突触和突触外 GABAAR 都对神经类固醇具有敏感性，并有助于神经类固醇调节中枢神经系统兴奋性的整体能力。酒精和神经类固醇对 GABAAR 的共同作用促进了对神经类固醇调节酒精急性和慢性作用能力的研究。将提供与实验结果相关的神经类固醇药理学和生物合成酶的背景。将总结关于酒精和神经类固醇跨神经解剖区域的相互作用以及中毒、消耗、依赖和戒断模型的数据。有证据支持急性饮酒后和戒断期间外周和大脑之间以及跨大脑区域的神经类固醇合成的独立调节。通过操纵神经类固醇合成来微调神经元兴奋性的局部机制对 GABAAR 介导的抑制发挥预测的行为和电生理反应。总的来说，针对神经类固醇生成可能是酒精使用障碍的有益治疗策略。
The term neurosteroid refers to rapid membrane actions of steroid hormones and their derivatives that can modulate physiological functions and behavior via their interactions with ligand-gated ion channels. This chapter will highlight recent advances pertaining to the modulatory effects of a select group of neurosteroids that are primarily potent positive allosteric modulators of γ-aminobutyric acidAreceptors (GABAARs). Nanomolar concentrations of neurosteroids, which occur in vivo, potentiate phasic and tonic forms of GABAAR-mediated inhibition, indicating that both synaptic and extrasynaptic GABAARs possess sensitivity to neurosteroids and contribute to the overall ability of neurosteroids to modulate central nervous system excitability. Common effects of alcohol and neurosteroids at GABAARs have stimulated research on the ability of neurosteroids to modulate alcohol’s acute and chronic effects. Background on neurosteroid pharmacology and biosynthetic enzymes will be provided as it relates to experimental findings. Data will be summarized on alcohol and neurosteroid interactions across neuroanatomical regions and models of intoxication, consumption, dependence, and withdrawal. Evidence supports independent regulation of neurosteroid synthesis between periphery and brain as well as across brain regions following acute alcohol administration and during withdrawal. Local mechanisms for fine-tuning neuronal excitability via manipulation of neurosteroid synthesis exert predicted behavioral and electrophysiological responses on GABAAR-mediated inhibition. Collectively, targeting neurosteroidogenesis may be a beneficial treatment strategy for alcohol use disorders.