Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects

Gwenn S. Smith, Ralf Schloesser, Jonathan D. Brodie, Stephen L. Dewey, Jean Logan, Stephen A. Vitkun, Philip Simkowitz, Arlene Hurley, Thomas Cooper, Nora D. Volkow, Robert Cancro

Research output: Contribution to journalArticlepeer-review

Abstract

Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, IV infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function.

Original languageEnglish (US)
Pages (from-to)18-25
Number of pages8
JournalNeuropsychopharmacology
Volume18
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • C-Raclopride
  • Dopamine
  • Glutamanate
  • Ketamine
  • Positron emission tomography

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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