Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach

Synapse. 1998 Jun;29(2):142-7. doi: 10.1002/(SICI)1098-2396(199806)29:2<142::AID-SYN5>3.0.CO;2-7.


Agents that antagonize the glutamatergic N-methyl-d-aspartate (NMDA) receptor, such as phenylcyclidine (PCP) and ketamine, produce a behavioral state in healthy volunteers that resembles some aspects of schizophrenia. A dysfunction in NMDA-dopaminergic interactions has been proposed as a mechanism for these behavioral effects. In this study, we examined the effects of ketamine on striatal dopamine release in healthy human subjects with a novel 11C-raclopride/PET displacement paradigm and compared these effects to administration of saline and the direct-acting dopamine agonist amphetamine. We found that the percent decreases (mean +/- SD) in specific 11C-raclopride binding from baseline for ketamine (11.2 +/- 8.9) was greater than for saline (1.9 +/- 3.7) (t = 2.4, df = 13, P = 0.003) indicating that ketamine caused increases in striatal synaptic dopamine concentrations. Ketamine-related binding changes were not significantly different than the decreases in percent change (mean +/- SD) in specific 11C-raclopride binding caused by amphetamine (15.5 +/- 6.2) (t = 1.3, df = 19, P = 0.21). Ketamine-induced changes in 11C-raclopride-specific binding were significantly correlated with induction of schizophrenia-like symptoms. The implications of this brain imaging method for studies of schizophrenia and the mechanism of action of antipsychotic drugs are discussed.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Amphetamine / pharmacology
  • Behavior / drug effects
  • Dopamine / metabolism*
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors / pharmacology
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • N-Methylaspartate / antagonists & inhibitors*
  • Neostriatum / diagnostic imaging
  • Neostriatum / metabolism*
  • Psychiatric Status Rating Scales
  • Psychoses, Substance-Induced / diagnostic imaging
  • Psychoses, Substance-Induced / psychology
  • Raclopride
  • Salicylamides
  • Tomography, Emission-Computed


  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Salicylamides
  • Raclopride
  • N-Methylaspartate
  • Amphetamine
  • Dopamine