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.
Key Words
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References
- Thinking glutamatergically: Changing concepts of schizophrenia based upon changing neurochemical models.Clin Schizophr Relat Psychoses. 2010; 4: 189-200
- Rapid onset of antidepressant action: A new paradigm in the research and treatment of major depressive disorder.J Clin Psychiatry. 2008; 69: 946-958
- Ketamine: Review of its pharmacology and its use in pediatric anesthesia.Anesth Prog. 1999; 46: 10-20
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate.Br J Pharmacol. 1983; 79: 565-575
- An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: A site of action of ketamine?.Nature. 1985; 313: 479-481
- Ketamine.Handb Exp Pharmacol. 2008; 182: 313-333
- Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.J Neurosci. 1997; 17: 2921-2927
- NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons.J Neurosci. 2007; 27: 11496-11500
- Regulation of neurotransmitter release by metabotropic glutamate receptors.J Neurochem. 2000; 75: 889-907
- Effects of a metabotropic glutamate receptor group II agonist LY354740 in animal models of positive schizophrenia symptoms and cognition.Behav Pharmacol. 2009; 20: 56-66
- Selective potentiation of the metabotropic glutamate receptor subtype 2 blocks phencyclidine-induced hyperlocomotion and brain activation.Neuroscience. 2010; 168: 209-218
- Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats.Science. 1998; 281: 1349-1352
- Awake rat pharmacological magnetic resonance imaging as a translational pharmacodynamic biomarker: Metabotropic glutamate 2/3 agonist modulation of ketamine-induced blood oxygenation level dependence signals.J Pharmacol Exp Ther. 2011; 336: 709-715
- Potential psychiatric applications of metabotropic glutamate receptor agonists and antagonists.CNS Drugs. 2010; 24: 669-693
- Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects.Psychopharmacology (Berl). 2005; 179: 303-309
- Cellular mechanisms underlying the antidepressant effects of ketamine: Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors.Biol Psychiatry. 2008; 63: 349-352
- mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.Science. 2010; 329: 959-964
- Involvement of AMPA receptor in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression.Behav Brain Res. 2011; 224: 107-111
- Neuronal-glial glucose oxidation and glutamatergic-GABAergic function.J Cereb Blood Flow Metab. 2006; 26: 865-877
- Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: Evidence for glial dysfunction and reduced glutamate/glutamine cycling.J Neurochem. 2007; 103: 2077-2091
- Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development.J Cereb Blood Flow Metab. 2007; 27: 1895-1907
- Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers.Am J Psychiatry. 1997; 154: 805-811
- The effect of ketamine isomers on both mice behavioral responses and c-Fos expression in the posterior cingulate and retrosplenial cortices.Brain Res. 2000; 857: 188-192
- Mapping the central effects of ketamine in the rat using pharmacological MRI.Psychopharmacology (Berl). 2006; 186: 64-81
- Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy: A [(123)I]CNS-1261 SPET study.Psychopharmacology (Berl). 2008; 197: 401-408
- Chronic administration of haloperidol and olanzapine attenuates ketamine-induced brain metabolic activation.J Pharmacol Exp Ther. 2003; 305: 999-1005
- Metabolic mapping of the rat brain after subanesthetic doses of ketamine: Potential relevance to schizophrenia.Brain Res. 1998; 787: 181-190
- Effects of ketamine, MK-801, and amphetamine on regional brain 2-deoxyglucose uptake in freely moving mice.Neuropsychopharmacology. 2000; 22: 400-412
- Blunted brain metabolic response to ketamine in mice lacking D(1A) dopamine receptors.Brain Res. 2001; 894: 167-180
- Glial pathology in an animal model of depression: Reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole.Mol Psychiatry. 2010; 15: 501-511
- The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo.Proc Natl Acad Sci U S A. 2005; 102: 5588-5593
- Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: A 4-T proton MRS study.Am J Psychiatry. 2005; 162: 394-396
- Lack of effect of ketamine on cortical glutamate and glutamine in healthy volunteers: A proton magnetic resonance spectroscopy study [published online ahead of print May 26].J Psychopharmacol. 2011;
- Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: An in vivo localized (1)H MRS study.NMR Biomed. 2009; 22: 737-744
Article info
Publication history
Published online: December 12, 2011
Accepted:
November 4,
2011
Received in revised form:
November 3,
2011
Received:
July 14,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
