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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Mar 22, 2016; 6(1): 31-42
Published online Mar 22, 2016. doi: 10.5498/wjp.v6.i1.31
Role of astrocytic glutamate transporter in alcohol use disorder
Jennifer R Ayers-Ringler, Yun-Fang Jia, Yan-Yan Qiu, Doo-Sup Choi
Jennifer R Ayers-Ringler, Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, United States
Yun-Fang Jia, Yan-Yan Qiu, Doo-Sup Choi, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
Author contributions: All authors contributed equally to conception and design of the manuscript, analysis and interpretation of data, drafting, and making critical revisions of the manuscript; all authors gave final approval of the version of the article to be published.
Supported by Mayo Graduate School, NIAAA, No. AA018779; SC Johnson Genomics of Addiction Program, Ulm Family Foundation, Center for Individualized Medicine at Mayo; and David Lehr Research Award from American Society for Pharmacology and Experimental Therapeutics.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Doo-Sup Choi, PhD, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, United States. choids@mayo.edu
Telephone: +1-507-2845602 Fax: +1-507-2841767
Received: August 29, 2015
Peer-review started: September 6, 2015
First decision: November 11, 2015
Revised: December 18, 2015
Accepted: January 8, 2016
Article in press: January 11, 2016
Published online: March 22, 2016
Processing time: 200 Days and 11.9 Hours
Abstract

Alcohol use disorder (AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol (measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from non-neuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD.

Keywords: Alcohol; Addiction; Glutamate; Astrocyte; Excitatory amino acid transporter type 2; Glia; Striatum

Core tip: Review of astroglial involvement in alcohol use disorder and potential for astrocyte-specific glutamate transporter excitatory amino acid transporter type 2 (EAAT2, Slc1a2)/GLT-1 in pharmacological treatment, including alcohol withdrawal symptoms.