Subanesthetic Ketamine Suppresses Locus Coeruleus-Mediated Alertness Effects: A 7T fMRI Study.
Thomas Liebe, Lena Vera Danyeli, Zümrüt Duygu Sen, Meng Li, Jörn Kaufmann, Martin Walter
The international journal of neuropsychopharmacology June 1, 2024 DOI: 10.1093/ijnp/pyae022 via PubMed
Summary
AI-generated from the abstractKetamine, an NMDA antagonist used as a rapid-acting antidepressant, disrupts the functional connectivity between the locus coeruleus (LC) and the thalamus, which is linked to a reduction in behavioral alertness. In a placebo-controlled, cross-over study with 35 healthy male participants (average age 25.1 years), ultra-high field 7T functional MRI revealed that acute disruption of the LC alertness network by ketamine correlates with decreased alertness. These findings highlight ketamine's effects beyond the glutamatergic system, suggesting a new mechanism involving noradrenergic pathways that may contribute to its antidepressant properties.
Study at a glance
| Characteristics | Placebo-controlled cross-over pharmacological MRI study Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Healthy male participants aged 25.1 ± 4.2 years |
| Intervention | S-ketamine |
| Topics | Ketamine |
| Keywords | Lc functional connectivity Locus coeruleus Ultra-High Field MRI Ketamine therapy Brain imaging |
| Citations | 5 |
| Key finding | Acute disruption of the locus coeruleus alertness network to the thalamus by ketamine is related to a behavioral alertness reduction. |
Abstract
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. 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. We could show that acute disruption of the LC alertness network to the thalamus by ketamine is related to a behavioral alertness reduction. 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.