Subanesthetic Ketamine Suppresses Locus Coeruleus-Mediated Alertness Effects: A 7T fMRI Study.

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-06-01 DOI:10.1093/ijnp/pyae022

Thomas Liebe, Lena Vera Danyeli, Zümrüt Duygu Sen, Meng Li, Jörn Kaufmann, Martin Walter

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Abstract

Background: The NMDA antagonist S-ketamine is gaining increasing use as a rapid-acting antidepressant, although its exact mechanisms of action are still unknown. In this study, we investigated ketamine in respect to its properties toward central noradrenergic mechanisms and how they influence alertness behavior.

Methods: We investigated the influence of S-ketamine on the locus coeruleus (LC) brain network in a placebo-controlled, cross-over, 7T functional, pharmacological MRI study in 35 healthy male participants (25.1 ± 4.2 years) in conjunction with the attention network task to measure LC-related alertness behavioral changes.

Results: We could show that acute disruption of the LC alertness network to the thalamus by ketamine is related to a behavioral alertness reduction.

Conclusion: The results shed new light on the neural correlates of ketamine beyond the glutamatergic system and underpin a new concept of how it may unfold its antidepressant effects.

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亚麻药氯胺酮可抑制由脑皮质介导的警觉效应--一项 7T fMRI 研究。

背景：NMDA拮抗剂氯胺酮（s-ketamine）作为一种速效抗抑郁剂的应用越来越广泛，但其确切的作用机制仍不清楚。在本研究中，我们研究了氯胺酮对中枢去甲肾上腺素能机制的特性及其如何影响警觉行为：方法：我们对35名健康男性参与者（25.1±4.2岁）进行了一项安慰剂对照、交叉、7T功能性、药理学磁共振成像研究，结合注意力网络任务，调查了氯胺酮对大脑小脑（LC）网络的影响，以测量与LC相关的警觉行为变化：结果：我们发现氯胺酮对丘脑的LC警觉网络的急性破坏与行为警觉性降低有关：结论：这些结果为氯胺酮在谷氨酸能系统之外的神经相关性提供了新的线索，并为氯胺酮如何发挥抗抑郁作用提供了新的概念。

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来源期刊

International Journal of Neuropsychopharmacology 医学-精神病学

CiteScore

8.40

自引率

2.10%

发文量

230

审稿时长

4-8 weeks

期刊介绍： The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.