Roles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites
Roles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites
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DOI：
10.1016/j.neuropharm.2022.109313
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发表时间：
2022-11-10
影响因子：
4.7
通讯作者：
Hashimoto, Hitoshi
中科院分区：
文献类型：
--
作者：
Ago, Yukio;Yokoyama, Rei;Hashimoto, Hitoshi
虽然（R，S）-氯胺酮（氯胺酮）的分子靶点被认为是NMDA受体，但已知亚麻醉剂量的氯胺酮可调节中枢神经系统中的单胺能神经传递。虽然在大多数关于这一主题的研究中已经报道了多巴胺能系统参与氯胺酮的抗抑郁作用，但最近的一些研究报道多巴胺能系统在氯胺酮的作用中起关键作用。此外，一些证据表明（R）-氯胺酮的抗抑郁样作用可能不依赖于单胺能系统。氯胺酮代谢物相对于（S）-氯胺酮和（R）-氯胺酮调节单胺神经递质的能力也存在差异，而（2 R，6 R）-羟基去甲氯胺酮可能与氯胺酮具有共同的多巴胺能信号传导机制。本文综述了氯胺酮及其代谢产物对脑内单胺神经传递的影响，并讨论了单胺能系统在氯胺酮作用机制中的潜在作用。
While the molecular target of (R,S)-ketamine (ketamine) is thought to be the NMDA receptor, subanesthetic doses of ketamine have been known to modulate monoaminergic neurotransmission in the central nervous system. Although the involvement of the serotonergic system in the antidepressant effects of ketamine has been reported in most studies of this topic, some recent studies have reported that the dopaminergic system plays a key role in the effects of ketamine. Additionally, several lines of evidence suggest that the antidepressant-like effects of (R)-ketamine might be independent of the monoaminergic system. Ketamine metabolites also differ consid-erably in their ability to regulate monoamine neurotransmitters relative to (S)-ketamine and (R)-ketamine, while (2R,6R)-hydroxynorketamine might share common serotonergic signaling mechanisms with ketamine. In the current review, we summarize the effects of ketamine and its metabolites on monoamine neurotransmission in the brain and discuss the potential roles of the monoaminergic system in the mechanism of action of ketamine.