Ketamine does not decrease striatal dopamine D2 receptor binding in man

Psychopharmacology (Berl). 2002 Dec;164(4):401-6. doi: 10.1007/s00213-002-1236-6. Epub 2002 Oct 12.


Rationale: A glutamate-dopamine interaction has been implicated in the psychosis-like effects of glutamate N-methyl- D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine. However, recent imaging studies addressing striatal glutamate-dopamine interaction directly in vivo in man have been controversial.

Objectives: To examine whether the NMDA receptor antagonist ketamine in high subanesthetic concentrations decreases striatal [(11)C]raclopride binding potential in man. To further evaluate whether changes in striatal [(11)C]raclopride binding are associated with ketamine-induced behavioral effects.

Methods: The effect of computer-driven subanesthetic ketamine infusion on striatal dopamine release was studied in healthy male subjects using a controlled study design. Dopamine release was studied using positron emission tomography and the [(11)C]raclopride displacement paradigm. A conventional region of interest-based analysis and voxel-based analysis were applied to the positron emission tomography data.

Results: The average plasma ketamine concentration was 293+/-29 ng/ml. Ketamine did not alter striatal [(11)C]raclopride binding. Ketamine induced typical behavioral effects, such as hallucinations but there was no correlation between these effects and displacement of [(11)C]raclopride binding.

Conclusions: This controlled study indicates that ketamine does not decrease striatal [(11)C]raclopride binding. Striatal dopamine release is of minor importance in the psychosis-like effects of ketamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Confusion / chemically induced
  • Confusion / diagnostic imaging
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects*
  • Dopamine / metabolism
  • Euphoria / drug effects
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Hallucinations / chemically induced
  • Hallucinations / diagnostic imaging
  • Humans
  • Image Processing, Computer-Assisted
  • Ketamine / pharmacology*
  • Male
  • Psychiatric Status Rating Scales
  • Raclopride / pharmacokinetics
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Tomography, Emission-Computed*


  • Excitatory Amino Acid Antagonists
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Raclopride
  • Ketamine
  • Dopamine