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

Alan Breier, Caleb M. Adler, Neil Weisenfeld, Tung Ping Su, Igor Elman, Lisa Picken, Anil K. Malhotra, David Pickar

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)142-147
Number of pages6
JournalSynapse
Volume29
Issue number2
DOIs
StatePublished - Jun 1 1998

Keywords

  • C-raclopride
  • Dopamine
  • Glutamate
  • NMDA
  • Positron emission tomography
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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