Strong Caroline E, Kabbaj Mohamed
Program in Neuroscience, Department of Biomedical Sciences, Florida State University, Tallahassee, FL, United States.
Front Behav Neurosci. 2020 Dec 10;14:593860. doi: 10.3389/fnbeh.2020.593860. eCollection 2020.
Alcohol use disorder (AUD) is the most prevalent substance use disorder and causes a significant global burden. Relapse rates remain incredibly high after decades of attempting to develop novel treatment options that have failed to produce increased rates of sobriety. Ketamine has emerged as a potential treatment for AUD following its success as a therapeutic agent for depression, demonstrated by several preclinical studies showing that acute administration reduced alcohol intake in rodents. As such, ketamine's therapeutic effects for AUD are now being investigated in clinical trials with the hope of it being efficacious in prolonging sobriety from alcohol in humans (ClinicalTrials.gov, Identifier: NCT01558063). Importantly, ketamine's antidepressant effects only last for about 1-week and because AUD is a lifelong disorder, repeated treatment regimens would be necessary to maintain sobriety. This raises questions regarding its safety for AUD treatment since ketamine itself has the potential for addiction. Therefore, this review aims to summarize the neuroadaptations related to alcohol's addictive properties as well as ketamine's therapeutic and addictive properties. To do this, the focus will be on reward-related brain regions such as the nucleus accumbens (NAc), dorsal striatum, prefrontal cortex (PFC), hippocampus, and ventral tegmental area (VTA) to understand how acute vs. chronic exposure will alter reward signaling over time. Additionally, evidence from these studies will be summarized in both male and female subjects. Accordingly, this review aims to address the safety of repeated ketamine infusions for the treatment of AUD. Although more work about the safety of ketamine to treat AUD is warranted, we hope this review sheds light on some answers about the safety of repeated ketamine infusions.
酒精使用障碍（AUD）是最普遍的物质使用障碍，给全球带来了沉重负担。在尝试开发新的治疗方案数十年后，复发率仍然高得惊人，这些方案未能提高戒酒率。氯胺酮已成为治疗AUD的一种潜在疗法，此前它作为一种治疗抑郁症的药物取得了成功，多项临床前研究表明，急性给药可减少啮齿动物的酒精摄入量。因此，目前正在临床试验中研究氯胺酮对AUD的治疗效果，希望它能有效延长人类戒酒时间（ClinicalTrials.gov，标识符：NCT01558063）。重要的是，氯胺酮的抗抑郁作用仅持续约1周，而由于AUD是一种终身疾病，需要重复治疗方案来维持戒酒。这就引发了关于其治疗AUD安全性的问题，因为氯胺酮本身就有成瘾的可能性。因此，本综述旨在总结与酒精成瘾特性以及氯胺酮治疗和成瘾特性相关的神经适应性变化。为此，重点将放在与奖赏相关的脑区，如伏隔核（NAc）、背侧纹状体、前额叶皮质（PFC）、海马体和腹侧被盖区（VTA），以了解急性与慢性暴露如何随时间改变奖赏信号。此外，这些研究在男性和女性受试者中的证据也将进行总结。因此，本综述旨在探讨重复输注氯胺酮治疗AUD的安全性。尽管关于氯胺酮治疗AUD安全性的更多研究仍有必要，但我们希望本综述能为重复输注氯胺酮的安全性提供一些答案。
