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

Author:

Oka Masahiro12,Yoshino Rui12,Kitanaka Nobue34,Hall F Scott56,Uhl George R78,Kitanaka Junichi12ORCID

Affiliation:

1. Laboratory of Drug Addiction and Experimental Therapeutics , Department of Pharmacy, School of Pharmacy, , 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530 , Japan

2. Hyogo Medical University , Department of Pharmacy, School of Pharmacy, , 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530 , Japan

3. Department of Pharmacology , School of Medicine, , Nishinomiya, Hyogo 663-8501 , Japan

4. Hyogo Medical University , School of Medicine, , Nishinomiya, Hyogo 663-8501 , Japan

5. Department of Pharmacology and Experimental Therapeutics , College of Pharmacy and Pharmaceutical Sciences, , Frederic and Mary Wolfe Center HEB 282D, Mail Stop 1015, 3000 Arlington Avenue,Toledo, OH 43614 , United States

6. University of Toledo , College of Pharmacy and Pharmaceutical Sciences, , Frederic and Mary Wolfe Center HEB 282D, Mail Stop 1015, 3000 Arlington Avenue,Toledo, OH 43614 , United States

7. Neurology Service, VA Maryland Healthcare System , 10 North Greene Street, Baltimore, MD 21201 , United States

8. Departments of Neurology and Pharmacology, University of Maryland School of Medicine , 655 W. Baltimore Street, Baltimore, MD 21201 , United States

Abstract

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.

Funder

Japan Society for the Promotion of Science

Publisher

Oxford University Press (OUP)

Subject

General Medicine

Reference90 articles.

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