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Subanesthetic S-ketamine does not acutely alter striatal dopamine transporter binding in healthy Sprague Dawley female rats

Lookup NU author(s): Emeritus Professor David Brooks

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Abstract

© 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.

Publication metadata

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

PubMed id: 38813759

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