Role of glycogen synthase kinase-3β in dependence and abuse liability of alcohol.

IF 2.1 4区医学 Q3 SUBSTANCE ABUSE

Alcohol and alcoholism Pub Date : 2024-01-17 DOI:10.1093/alcalc/agad086

Masahiro Oka, Rui Yoshino, Nobue Kitanaka, F Scott Hall, George R Uhl, Junichi Kitanaka

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引用次数: 0

Abstract

Background: Alcohol is a major abused drug worldwide that contributes substantially to health and social problems. These problems result from acute alcohol overuse as well as chronic use, leading to alcohol use disorder (AUD). A major goal of this field is to establish a treatment for alcohol abuse and dependence in patients with AUD. The central molecular mechanisms of acute alcohol actions have been extensively investigated in rodent models.

Aims: One of the central mechanisms that may be involved is glycogen synthase kinase-3β (GSK-3β) activity, a key enzyme involved in glycogen metabolism but which has crucial roles in numerous cellular processes. Although the exact mechanisms leading from acute alcohol actions to these chronic changes in GSK-3β function are not yet clear, GSK-3β nonetheless constitutes a potential therapeutic target for AUD by reducing its function using GSK-3β inhibitors. This review is focused on the correlation between GSK-3β activity and the degree of alcohol consumption.

Methods: Research articles regarding investigation of effect of GSK-3β on alcohol consumption in rodents were searched on PubMed, Embase, and Scopus databases using keywords "glycogen synthase kinase," "alcohol (or ethanol)," "intake (or consumption)," and evaluated by changes in ratios of pGSK-3βSer9/pGSK-3β.

Results: In animal experiments, GSK-3β activity decreases in the brain under forced and voluntary alcohol consumption while GSK-3β activity increases under alcohol-seeking behavior.

Conclusions: Several pieces of evidence suggest that alterations in GSK-3β function are important mediators of chronic ethanol actions, including those related to alcohol dependence and the adverse effects of chronic ethanol exposure.

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糖原合酶激酶-3β在酒精依赖和滥用中的作用

背景：酒精是世界范围内的主要滥用药物，对健康和社会问题有重大影响。这些问题源于急性酒精过度使用和慢性使用，从而导致酒精使用障碍（AUD）。该领域的一个主要目标是建立针对酒精滥用和酒精依赖症患者的治疗方法。目的：可能涉及的核心机制之一是糖原合酶激酶-3β（GSK-3β）的活性，这是一种参与糖原代谢的关键酶，但在许多细胞过程中都发挥着重要作用。虽然从急性酒精作用到 GSK-3β 功能的慢性变化的确切机制尚不清楚，但通过使用 GSK-3β 抑制剂降低其功能，GSK-3β 已成为治疗 AUD 的潜在靶点。本综述主要关注 GSK-3β 活性与饮酒程度之间的相关性：方法：使用关键词 "糖原合酶激酶"、"酒精（或乙醇）"、"摄入量（或消费量）"在 PubMed、Embase 和 Scopus 数据库中检索有关 GSK-3β 对啮齿动物饮酒影响的研究文章，并通过 pGSK-3βSer9/pGSK-3β 的比率变化进行评估：结果：在动物实验中，在强迫和自愿饮酒的情况下，大脑中 GSK-3β 的活性会降低，而在寻求酒精的行为下，GSK-3β 的活性会升高：结论：多项证据表明，GSK-3β功能的改变是慢性乙醇作用的重要介质，包括与酒精依赖和慢性乙醇暴露的不良影响有关的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcohol and alcoholism 医学-药物滥用

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

4-8 weeks

期刊介绍： About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.