title: Ketamine does not decrease striatal dopamine D2 receptor binding in man.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Neuropsychiatric Imaging, Turku PET Centre, Turku University Central Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
authors.forename: Sargo
authors.initials: S
authors.lastname: Aalto
authors.forename: Jussi
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Jaana
authors.initials: J
authors.lastname: Kajander
authors.forename: Harry
authors.initials: H
authors.lastname: Scheinin
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.forename: Harry
authors.initials: H
authors.lastname: Vilkman
authors.forename: Lars
authors.initials: L
authors.lastname: Gustafsson
authors.forename: Erkka
authors.initials: E
authors.lastname: Syvälahti
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
mesh_terms: D000328:Adult; D003221:Confusion / Q000139:chemically induced / Q000000981:diagnostic imaging; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D005059:Euphoria / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006212:Hallucinations / Q000139:chemically induced / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D011569:Psychiatric Status Rating Scales; D020891:Raclopride / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D014055:Tomography, Emission-Computed
chemical_list: D018691:Excitatory Amino Acid Antagonists; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D020891:Raclopride; D007649:Ketamine; D004298:Dopamine