H-[¹³C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism

• Published in: Biological psychiatry (1969) 2012-06, Vol.71 (11), p.1022-1025
• Main Authors: Chowdhury, Golam M I, Behar, Kevin L, Cho, William, Thomas, Monique A, Rothman, Douglas L, Sanacora, Gerard
• Format: Article
• Language: English
• Subjects: Affect - drug effects; Animals; Carbon Isotopes; Cognition - drug effects; Excitatory Amino Acid Antagonists - pharmacology; gamma-Aminobutyric Acid - drug effects; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - drug effects; Glutamic Acid - metabolism; Glutamine - drug effects; Glutamine - metabolism; Hippocampus - diagnostic imaging; Hippocampus - drug effects; Hippocampus - metabolism; Hydrogen; Ketamine - pharmacology; Magnetic Resonance Spectroscopy - methods; Male; Neuroglia - drug effects; Neuroglia - metabolism; Neurotransmitter Agents - metabolism; Perception - drug effects; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Radionuclide Imaging; Rats; Rats, Sprague-Dawley
• ISSN: 1873-2402
• DOI: 10.1016/j.biopsych.2011.11.006

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.