Subanesthetic Ketamine Suppresses Locus Coeruleus-Mediated Alertness Effects: A 7T fMRI Study
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 alertn...
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| Veröffentlicht in: | The international journal of neuropsychopharmacology 2024-06, Vol.27 (6), p.1 |
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| container_title | The international journal of neuropsychopharmacology |
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| creator | Liebe, Thomas Danyeli, Lena Vera Sen, Zumrut Duygu Li, Meng Kaufmann, Jorn Walter, Ma |
| description | 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 [+ or -] 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. Keywords: Ketamine, locus coeruleus, LC functional connectivity, alertness, ultra-high field MRI |
| doi_str_mv | 10.1093/iinp/pyae022 |
| format | Article |
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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 [+ or -] 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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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 [+ or -] 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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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 [+ or -] 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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| subjects | Alertness (Psychology) Analysis Dosage and administration Health aspects Ketamine Locus coeruleus Magnetic resonance imaging |
| title | Subanesthetic Ketamine Suppresses Locus Coeruleus-Mediated Alertness Effects: A 7T fMRI Study |
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