title: ¹H-[¹³C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism.
abstract: 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.
authors.affiliation: Department of Psychiatry and the Ribicoff Research Facilities, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA. golam.chowdhury@yale.edu
authors.forename: Golam M I
authors.initials: GM
authors.lastname: Chowdhury
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Behar
authors.forename: William
authors.initials: W
authors.lastname: Cho
authors.forename: Monique A
authors.initials: MA
authors.lastname: Thomas
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
mesh_terms: D000339:Affect / Q000187:drug effects; D000818:Animals; D002247:Carbon Isotopes; D003071:Cognition / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006859:Hydrogen; D007649:Ketamine / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010465:Perception / Q000187:drug effects; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D006859:Hydrogen