Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study.
OBJECTIVE
The authors' goal was to test in humans the hypothesis that N-methyl-d-aspartate receptor (NMDAR) antagonism results in increased cortical glutamate activity, as proposed by the NMDAR hypofunction model of schizophrenia.


METHODS
4-T 1H proton magnetic resonance spectroscopy (1H-MRS) was used to acquire in vivo spectra from the bilateral anterior cingulate of 10 healthy subjects while they received a subanesthetic dose of either placebo or ketamine, an NMDAR antagonist. Assessments given before and after ketamine or placebo administration included the Brief Rating Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Clinician-Administered Dissociative States Scale, and the Stroop task.


RESULTS
As predicted, there was a significant increase in anterior cingulate glutamine, a putative marker of glutamate neurotransmitter release, with ketamine administration. This increase was not related to schizophrenia-like positive or negative symptoms but was marginally related to Stroop performance.


CONCLUSIONS
In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate.
Rowland
Laura M
LM
Department of Psychiatry, MIND Imaging Center, University of New Mexico, USA. lrowland@mprc.umaryland.edu
Bustillo
Juan R
JR
Mullins
Paul G
PG
Jung
Rex E
RE
Lenroot
Rhoshel
R
Landgraf
Elma
E
Barrow
Ranee
R
Yeo
Ronald
R
Lauriello
John
J
Brooks
William M
WM
D000328:Adult; D010054:Brief Psychiatric Rating Scale; D018592:Cross-Over Studies; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005971:Glutamates / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine