NMDA antagonist effects on striatal dopamine release: Microdialysis studies in awake monkeys

Barbara W. Adams, Charles W. Bradberry, Bita Moghaddam

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Brain imaging studies have suggested that the NMDA antagonist ketamine is as potent a releaser of striatal dopamine as amphetamine. This conclusion contradicts microdialysis findings in the rodent that NMDA antagonists, in contrast to amphetamine, have little or no effect on striatal dopamine release. The present study addressed two mechanisms that could account for this discrepancy: 1) whether there is a species difference, i.e., rodents vs. primates, in the responsivity of striatal dopamine to NMDA antagonists, and 2) whether rapid uptake of dopamine prevents reliable measures of synaptic dopamine release by microdialysis in response to NMDA antagonists. MRI-directed in vivo microdialysis was used to compare the effects of psychotomimetic NMDA antagonists phencyclidine (PCP), ketamine, and amphetamine on extracellular striatal dopamine levels in awake rhesus monkeys. The effect of PCP was also investigated in the presence of intrastriatally applied nomifensine, a dopamine uptake blocker. Amphetamine (0.1 or 0.4 mg/kg) produced robust and dose-dependent increases in dopamine release ranging 2-10-fold above baseline. PCP at 0.1 mg/kg had no effect and at 0.3 mg/kg produced a small 50% increase over baseline. Ketamine, at the relatively high dose of 5 mg/kg, produced only a 30% increase in dopamine release. Intrastriatal application of nomifensine did not influence the effect of PCP, suggesting that rapid uptake of dopamine is not preventing the detection of a PCP-induced increase in dopamine release. These findings suggest that in the primate, ketamine and PCP are not effective dopamine releasers, as has been suggested by previous imaging studies.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalSynapse
Volume43
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Amphetamine
  • Ketamine
  • Microdialysis
  • Phencyclidine
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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