Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study

Am J Psychiatry. 2005 Feb;162(2):394-6. doi: 10.1176/appi.ajp.162.2.394.


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.

Method: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Brief Psychiatric Rating Scale
  • Cross-Over Studies
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glutamates / drug effects
  • Glutamates / metabolism*
  • Glutamates / physiology
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / metabolism*
  • Humans
  • Ketamine / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Male
  • Neuropsychological Tests
  • Placebos
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Schizophrenia / chemically induced
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology


  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Placebos
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine