Jennifer R Ayers-Ringler, Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, United States.
World J Psychiatry. 2016 Mar 22;6(1):31-42. doi: 10.5498/wjp.v6.i1.31.
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.
酒精使用障碍（AUD）是最普遍的神经精神疾病之一，对健康和社会经济有重大影响。根据 2014 年世界卫生组织全球酒精和健康状况报告，全世界有 5.9%的死亡归因于有害使用酒精。此外，全球 5.1%的疾病和伤害负担归因于酒精（以残疾调整生命年或残疾调整生命年来衡量）。尽管 AUD 的神经生物学基础非常复杂，但皮质纹状体回路对成瘾行为的发展有重要贡献。深入研究 AUD 及其他成瘾中该回路中神经递质的变化，如多巴胺、γ-氨基丁酸和谷氨酸，以及它们对应的神经元受体，使我们能够了解 AUD 的分子基础。然而，这些发现也揭示了非神经元来源的贡献知识的匮乏。星形胶质细胞虽然与突触功能密切相关，但直到最近才在 AUD 中的潜在作用中明显被忽视。星形胶质细胞的一个主要功能是通过兴奋性氨基酸转运蛋白 2 将谷氨酸从突触中清除，从而保护神经元免受兴奋性毒性。该关键转运蛋白在成瘾以及乙醇戒断中的重要性最近已经变得明显，尽管其调节仍在研究中。从历史上看，AUD 的药物治疗一直集中在改变神经元谷氨酸受体的活性上。然而，最近的临床证据支持了基于动物的发现，表明调节谷氨酸稳态有助于成功管理 AUD 的康复。
