Ketamine does not decrease striatal dopamine D2 receptor binding in man

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 [C-11]raclopride binding potential in man. To further evaluate whether changes in striatal [C-11]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 [C-11]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 [C-11]raclopride binding. Ketamine induced typical behavioral effects, such as hallucinations but there was no correlation between these effects and displacement of [C-11]raclopride binding. Conclusions: This controlled study indicates that ketamine does not decrease striatal [C-11]raclopride binding. Striatal dopamine release is of minor importance in the psychosis-like effects of ketamine.