Neural Mechanisms Underlying the Rewarding and Therapeutic Effects of Ketamine as a Treatment for Alcohol Use Disorder.
Neural Mechanisms Underlying the Rewarding and Therapeutic Effects of Ketamine as a Treatment for Alcohol Use Disorder.
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DOI：
10.3389/fnbeh.2020.593860
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发表时间：
2020
影响因子：
3
通讯作者：
Kabbaj M
中科院分区：
文献类型：
--
作者：
Strong CE;Kabbaj M
酒精使用障碍（AUD）是最普遍的物质使用障碍，并造成重大的全球负担。几十年来，人们一直试图开发新的治疗方案，但未能提高清醒率，复发率仍然非常高。氯胺酮在成功作为抑郁症治疗药物后已成为AUD的潜在治疗药物，几项临床前研究表明，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的治疗作用，希望它能有效延长人类酒精的清醒时间（ClinicalTrials.gov，标识符：NCT 01558063）。重要的是，氯胺酮的抗抑郁作用仅持续约1周，并且由于AUD是一种终身疾病，因此需要重复治疗方案来保持清醒。这引发了关于其用于AUD治疗的安全性的问题，因为氯胺酮本身具有成瘾的可能性。因此，本文综述了与酒精成瘾特性相关的神经适应以及氯胺酮的治疗和成瘾特性。为了做到这一点，重点将放在奖励相关的大脑区域，如背侧纹状体（NAc），前额叶皮层（PFC），海马和腹侧被盖区（VTA），以了解急性与慢性暴露如何随着时间的推移改变奖励信号。此外，将在男性和女性受试者中总结这些研究的证据。因此，本综述旨在探讨氯胺酮重复输注治疗AUD的安全性。虽然有必要对氯胺酮治疗AUD的安全性进行更多的研究，但我们希望这篇综述能够揭示关于重复氯胺酮输注安全性的一些答案。
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.
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DOI：
10.1038/npp.2008.144
发表时间：
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期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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