title: Role of astrocytic glutamate transporter in alcohol use disorder.
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.
authors.affiliation: Jennifer R Ayers-Ringler, Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Ayers-Ringler
authors.affiliation: Jennifer R Ayers-Ringler, Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Jia
authors.affiliation: Jennifer R Ayers-Ringler, Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Qiu
authors.affiliation: Jennifer R Ayers-Ringler, Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
keywords: Addiction; Alcohol; Astrocyte; Excitatory amino acid transporter type 2; Glia; Glutamate; Striatum