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胃饥饿素/生长激素释放肽受体1A信号通路在非酒精性药物成瘾中的作用

The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions.

作者信息

Sustkova-Fiserova Magdalena, Charalambous Chrysostomos, Khryakova Anna, Certilina Alina, Lapka Marek, Šlamberová Romana

机构信息

Department of Pharmacology, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic.

Department of Physiology, Third Faculty of Medicine, Charles University, Ke Karlovu 4, 120 00 Prague, Czech Republic.

出版信息

Int J Mol Sci. 2022 Jan 11;23(2):761. doi: 10.3390/ijms23020761.

Abstract

Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin's/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin's/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

摘要

药物成瘾给人类社会带来了持续严重的健康、社会和经济负担。目前的药物依赖性药物治疗,尤其是预防复发的治疗,仍然有限、不尽人意,对阿片类药物和烟草不可靠,对兴奋剂和大麻素甚至只是对症治疗,因此,人们正在研究更新更有效的治疗策略。最近有人提出,拮抗A型生长激素促分泌素受体(GHS-R1A)是一种新型的酒精成瘾治疗策略,并且已经在尼古丁、兴奋剂、阿片类药物和大麻素等其他成瘾药物的实验模型中进行了深入研究。胃饥饿素信号传导在这些药物作用中的作用也已得到研究。本综述旨在全面概述临床前和临床研究,这些研究聚焦于胃饥饿素/GHS-R1A可能参与这些非酒精成瘾药物的强化作用和成瘾过程。尽管研究仍处于早期阶段,但现有大多数来自啮齿动物的实验结果加上少数人体研究(这些研究探寻了胃饥饿素信号传导的基因变异或胃饥饿素血液含量与成瘾药物作用之间的相关性)表明,胃饥饿素/GHS-R1A参与非酒精滥用药物的促成瘾作用具有重要意义。有必要进一步研究以阐明确切的相关机制,并验证GHS-R1A拮抗作用在这些药物成瘾治疗中的未来潜在应用和安全性,特别是在降低复发风险方面。

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The growth hormone secretagogue receptor (Ghs-R).生长激素促分泌素受体(Ghs-R)。
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