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Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial
There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies atte...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579356/ https://www.ncbi.nlm.nih.gov/pubmed/37231079 http://dx.doi.org/10.1038/s41386-023-01605-4 |
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author | Gärtner, Matti Weigand, Anne Meiering, Marvin Sören Weigner, David Carstens, Luisa Keicher, Christian Hertrampf, Rita Beckmann, Christian Mennes, Maarten Wunder, Andreas Grimm, Simone |
author_facet | Gärtner, Matti Weigand, Anne Meiering, Marvin Sören Weigner, David Carstens, Luisa Keicher, Christian Hertrampf, Rita Beckmann, Christian Mennes, Maarten Wunder, Andreas Grimm, Simone |
author_sort | Gärtner, Matti |
collection | PubMed |
description | There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies attempting to characterize ketamine’s mechanism of action by using blood oxygen level dependent (BOLD) imaging have yielded inconsistent results regarding implicated brain regions and direction of effects. This may be due to intrinsic properties of the BOLD contrast, while cerebral blood flow (CBF), as measured with arterial spin labeling, is a single physiological marker more directly related to neural activity. As effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release, a combination of these approaches should be particularly suited to offer novel insights. In total, 75 healthy participants were investigated in a double blind, placebo-controlled, randomized, parallel-group study and underwent two scanning sessions (acute/post 24 h.). Acute ketamine administration was associated with higher perfusion in interior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC), but no other investigated brain region. Inhibition of glutamate release by pretreatment with lamotrigine abolished ketamine’s effect on perfusion. At the delayed time point, pretreatment with lamotrigine was associated with lower perfusion in IFG. These findings underscore the idea that regionally selective patterns of CBF changes reflect proximate effects of modulated glutamate release on neuronal activity. Furthermore, region- specific sustained effects indicate both a swift restoration of disturbed homeostasis in DLPFC as well changes occurring beyond the immediate effects on glutamate signaling in IFG. |
format | Online Article Text |
id | pubmed-10579356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-105793562023-10-18 Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial Gärtner, Matti Weigand, Anne Meiering, Marvin Sören Weigner, David Carstens, Luisa Keicher, Christian Hertrampf, Rita Beckmann, Christian Mennes, Maarten Wunder, Andreas Grimm, Simone Neuropsychopharmacology Article There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies attempting to characterize ketamine’s mechanism of action by using blood oxygen level dependent (BOLD) imaging have yielded inconsistent results regarding implicated brain regions and direction of effects. This may be due to intrinsic properties of the BOLD contrast, while cerebral blood flow (CBF), as measured with arterial spin labeling, is a single physiological marker more directly related to neural activity. As effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release, a combination of these approaches should be particularly suited to offer novel insights. In total, 75 healthy participants were investigated in a double blind, placebo-controlled, randomized, parallel-group study and underwent two scanning sessions (acute/post 24 h.). Acute ketamine administration was associated with higher perfusion in interior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC), but no other investigated brain region. Inhibition of glutamate release by pretreatment with lamotrigine abolished ketamine’s effect on perfusion. At the delayed time point, pretreatment with lamotrigine was associated with lower perfusion in IFG. These findings underscore the idea that regionally selective patterns of CBF changes reflect proximate effects of modulated glutamate release on neuronal activity. Furthermore, region- specific sustained effects indicate both a swift restoration of disturbed homeostasis in DLPFC as well changes occurring beyond the immediate effects on glutamate signaling in IFG. Springer International Publishing 2023-05-25 2023-11 /pmc/articles/PMC10579356/ /pubmed/37231079 http://dx.doi.org/10.1038/s41386-023-01605-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gärtner, Matti Weigand, Anne Meiering, Marvin Sören Weigner, David Carstens, Luisa Keicher, Christian Hertrampf, Rita Beckmann, Christian Mennes, Maarten Wunder, Andreas Grimm, Simone Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
title | Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
title_full | Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
title_fullStr | Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
title_full_unstemmed | Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
title_short | Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
title_sort | region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579356/ https://www.ncbi.nlm.nih.gov/pubmed/37231079 http://dx.doi.org/10.1038/s41386-023-01605-4 |
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