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Lookup NU author(s): Emeritus Professor David Brooks
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2024 The Author(s). Synapse published by Wiley Periodicals LLC.Major depressive disorder is one of the most prevalent mental health disorders, posing a global socioeconomic burden. Conventional antidepressant treatments have a slow onset of action, and 30% of patients show no clinically significant treatment response. The recently approved fast-acting antidepressant S-ketamine, an N-methyl-D-aspartate receptor antagonist, provides a new approach for treatment-resistant patients. However, knowledge of S-ketamine's mechanism of action is still being established. Depressed human subjects have lower striatal dopamine transporter (DAT) availability compared to healthy controls. Rodent studies report increased striatal dopamine concentration in response to acute ketamine administration. In vivo [18F]FE-PE2I ([18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4′-methyl-phenyl) nortropane) positron emission tomography (PET) imaging of the DAT has not previously been applied to assess the effect of acute subanesthetic S-ketamine administration on DAT availability. We applied translational in vivo [18F]FE-PE2I PET imaging of the DAT in healthy female rats to evaluate whether an acute subanesthetic intraperitoneal dose of 15 mg/kg S-ketamine alters DAT availability. We also performed [3H]GBR-12935 autoradiography on postmortem brain sections. We found no effect of acute S-ketamine administration on striatal DAT binding using [18F]FE-PE2I PET or [3H]GBR-12935 autoradiography. This negative result does not support the hypothesis that DAT changes are associated with S-ketamine's rapid antidepressant effects, but additional studies are warranted.
Author(s): Baerentzen SL, Thomsen JB, Thomsen MB, Jakobsen S, Simonsen MT, Wegener G, Brooks DJ, Landau AM
Publication type: Article
Publication status: Published
Journal: Synapse
Year: 2024
Volume: 78
Issue: 4
Print publication date: 01/07/2024
Online publication date: 30/05/2024
Acceptance date: 10/05/2024
Date deposited: 10/06/2024
ISSN (print): 0887-4476
ISSN (electronic): 1098-2396
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/syn.22294
DOI: 10.1002/syn.22294
Data Access Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
PubMed id: 38813759
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