Subanesthetic S-ketamine does not acutely alter striatal dopamine transporter binding in healthy Sprague Dawley female rats.
Simone Larsen Bærentzen, Jakob Borup Thomsen, Majken Borup Thomsen, Steen Jakobsen, Mette Theilgaard Simonsen, Gregers Wegener, David J Brooks, Anne M Landau
Synapse July 1, 2024 DOI: 10.1002/syn.22294 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Translational in vivo imaging with autoradiography Peer reviewed |
|---|---|
| Population | Healthy female rats |
| Intervention | S-ketamine |
| Dose | 15 mg/kg |
| Duration | Acute administration |
| Topics | Ketamine Esketamine |
| Keywords | Gbr‐12935 Pe2i S‐ketamine Dopamine transporter dat Fast‐acting antidepressant Antidepressants s-ketamine Fast-acting antidepressants Brain Imaging PET Positron emission tomography Neuroimaging Dopamine dat |
| Citations | 1 |
| Key points | Acute subanesthetic S-ketamine administration had no effect on striatal DAT binding in healthy female rats. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cites 11
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects Molecular Psychiatry February 27, 2018
- The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders Molecular Psychiatry October 3, 2017
- Ketamine: A tale of two enantiomers Journal of Psychopharmacology November 6, 2020
and 6 more in the library