The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects

The ability of ketamine administration to activate prefrontal glutamate neurotransmission is thought to be a key mechanism contributing to its transient psychotomimetic effects and its delayed and sustained antidepressant effects. Rodent studies employing carbon-13 magnetic resonance spectroscopy (...

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Vydáno v:Neuropsychopharmacology (New York, N.Y.) Ročník 43; číslo 10; s. 2154 - 2160
Hlavní autoři: Abdallah, Chadi G, De Feyter, Henk M, Averill, Lynnette A, Jiang, Lihong, Averill, Christopher L, Chowdhury, Golam M I, Purohit, Prerana, de Graaf, Robin A, Esterlis, Irina, Juchem, Christoph, Pittman, Brian P, Krystal, John H, Rothman, Douglas L, Sanacora, Gerard, Mason, Graeme F
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.09.2018
Témata:
Adult
Aged
Antidepressive Agents - pharmacology
Carbon 13
Cortex (frontal)
Depressive Disorder - physiopathology
Energy Metabolism - drug effects
Excitatory Amino Acid Antagonists - pharmacology
Female
Glutamate receptors
Glutamates - physiology
Glutamic acid receptors (ionotropic)
Glutamine
Hallucinogens - pharmacology
Healthy Volunteers
Humans
Ketamine
Ketamine - pharmacology
Magnetic Resonance Spectroscopy
Male
Mental disorders
Middle Aged
N-Methyl-D-aspartic acid receptors
Neurotransmission
Pilot Projects
Prefrontal cortex
Prefrontal Cortex - drug effects
Prefrontal Cortex - metabolism
Rodents
Schizophrenia
Synaptic Transmission - drug effects
Young Adult
ISSN:0893-133X, 1740-634X, 1740-634X
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Shrnutí:The ability of ketamine administration to activate prefrontal glutamate neurotransmission is thought to be a key mechanism contributing to its transient psychotomimetic effects and its delayed and sustained antidepressant effects. Rodent studies employing carbon-13 magnetic resonance spectroscopy ( 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. However, there are not yet direct measures of glutamate neurotransmission in vivo in humans to support these hypotheses. The current first-level pilot study employed a novel prefrontal C MRS approach similar to that used in the rodent studies for direct measurement of ketamine effects on glutamate-glutamine cycling. Twenty-one participants (14 healthy and 7 depressed) completed two C MRS scans during infusion of normal saline or subanesthetic doses of ketamine. Compared to placebo, ketamine increased prefrontal glutamate-glutamine cycling, as indicated by a 13% increase in C glutamine enrichment (t = 2.4, p = 0.02). We found no evidence of ketamine effects on oxidative energy production, as reflected by C glutamate enrichment. During ketamine infusion, the ratio of C glutamate/glutamine enrichments, a putative measure of neurotransmission strength, was correlated with the Clinician-Administered Dissociative States Scale (r = -0.54, p = 0.048). These findings provide the most direct evidence in humans to date that ketamine increases glutamate release in the prefrontal cortex, a mechanism previously linked to schizophrenia pathophysiology and implicated in the induction of rapid antidepressant effects.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0893-133X
1740-634X
1740-634X
DOI:10.1038/s41386-018-0136-3