1H-[13C]-Nuclear Magnetic Resonance Spectroscopy Measures of Ketamine's Effect on Amino Acid Neurotransmitter Metabolism
Open accessAbstract
Ketamine has recently gained significant attention owing to its psychotomimetic and more recently discovered rapid antidepressant-like properties. ¹H-[¹³C]-nuclear magnetic resonance studies were employed to explore potential physiological processes underlying these unique effects. [1-¹³C]glucose and [2-¹³C]acetate-nuclear magnetic resonance ex vivo studies were performed on the medial prefrontal cortex (mPFC) and hippocampus of rats acutely treated with 30 mg/kg or 80 mg/kg ketamine and compared with saline-treated animals to determine the effects of ketamine on amino acid neurotransmitter cycling and glial metabolism. A subanesthetic, but not anesthetic, dose of ketamine significantly increased the percentage of ¹³C-enrichments of glutamate, γ-aminobutyric acid, and glutamine in the mPFC of rats. Subanesthetic doses of ketamine increased mPFC amino acid neurotransmitter cycling, as well as neuronal and glial energy metabolism. These data add to previous reports suggesting increased mPFC levels of glutamate release, following the administration of subanesthetic doses of ketamine, are related to the drug's acute effects on cognition, perception, and mood.
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Rodent studies have shown that ketamine and other NMDA receptor antagonists transiently increase measures reflecting glutamate-glutamine cycling and glutamate neurotransmission in the frontal cortex.
“Rodent studies employing carbon-13 magnetic resonance spectroscopy ( 13 C MRS) methods have shown ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists to transiently increase measures reflecting glutamate-glutamine cycling and glutamate neurotransmission in the frontal cortex.”
From The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (2018) · cites this paper as [16]
The Discussion (page not supplied) reports that subanesthetic ketamine acutely increased carbon-13 labeling of glutamate and glutamine in rodent medial prefrontal cortex, suggesting increased glutamate–glutamine cycling. The paper did not use these spectroscopy methods to show the same effect for other NMDA receptor antagonists; its Introduction instead discusses transient glutamate increases reported by microdialysis studies. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe approach parallels extant preclinical data, which facilitates the translatability of the biomarker between species.
“The approach parallels extent preclinical data [16,17], which facilitates the translatability of the biomarker between species.”
From The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (2018) · cites this paper as [16]
The Discussion (page unavailable) reports that ketamine increased glutamate-related cycling in rats, consistent with earlier preclinical studies. It does not establish that the biomarker translates between species; instead, it says species and methodological differences limit comparisons across studies. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPreclinical 13C MRS data suggest disproportionate changes following ketamine administration.
“While these processes are highly coupled under normal conditions, preclinical 13 C MRS data suggest disproportionate changes following ketamine administration [16,17].”
From The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects (2018) · cites this paper as [16]
The Results and Discussion report that subanesthetic ketamine increased 13C labeling of glutamate, glutamine, and GABA in rat medial prefrontal cortex, suggesting increases in neurotransmitter cycling and oxidative metabolism. The passages do not establish that the changes in these coupled processes were disproportionate to one another. (LLM, conf=0.78)
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- Authors
- Chowdhury, G. M. I., Behar, K. L., Cho, W., Thomas, M. A., Rothman, D. L., & Sanacora, G.
- Affiliations
- Yale University (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Chowdhury, Golam M.I.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 71
- Issue
- 11
- Pages
- 1022-1025
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3660962
- OpenAlex
- W1971460793
- Cited by
- 125
- References
- 34
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 14 · 2021: 7 · 2020: 11 · 2019: 10 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 14 · 2014: 11 · 2013: 7 · 2012: 5
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r01mh095104-01)
- National Institute of Mental Health (R01MH081211, 1R01 MH095104, R01-MH095104)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ketamine, amino acid neurotransmitters, glutamate, GABA, glutamine, medial prefrontal cortex, hippocampus, subanesthetic doses, rapid antidepressant effects, psychotomimetic effects, glial metabolism, neuronal energy metabolism, glutamate release, 13C metabolic labeling
- MeSH terms
- Affect, Animals, Carbon Isotopes, Cognition, gamma-Aminobutyric Acid, Glutamine, Hippocampus, Hydrogen, Ketamine, Male, Neuroglia, Magnetic Resonance Spectroscopy, Perception, Radionuclide Imaging, Rats, Sprague-Dawley, Prefrontal Cortex, Neurotransmitter Agents, Excitatory Amino Acid Antagonists, Glutamic Acid, Rats
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