Phencyclidine produces changes in NMDA and kainate receptor binding in rat hippocampus over a 48-hour time course

Xue Min Gao, Carol A. Tamminga

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Phencyclidine (PCP) is a psychotomimetic drug associated with acute and delayed mental effects in normal humans and psychosis exacerbation in already psychotic schizophrenic individuals. We have previously described a dose-sensitive, delayed action of PCP on regional cerebral metabolism in the rat which occurs over 48 hours and a late (24 hour) change in N-methyl-d- aspartate (NMDA) and kainate binding in hippocampal areas. Now, we report the complex time course of PCP action on NMDA-sensitive glutamate receptor binding in rat in distinct subregions of the hippocampus extending over 48 hours. Selectively, in the hippocampal CA, region, a single dose of PCP (8.6 mg/kg) produced an increase in receptor binding at 12 hours (+24%), sustained to 24 hours (+29%) compared with the 3 hour post-PCP value (-15%) and then a return to control levels of receptor binding at 48 hours. Other regions of hippocampus showed distinctive time-dependent changes in NMDA- sensitive glutamate receptor binding as well. In addition, PCP produced a change in kainate receptor binding in the dentate gyrus across the 48-hour time period. In other representative brain regions, PCP did not alter NMDA or kainate binding over the same time course. This extended neurochemical effect of PCP on glutamate receptors in rat hippocampus parallels, in time, certain delayed psychological actions of PCP in humans and thus may be relevant to psychosis, especially to PCP-induced psychosis.

Original languageEnglish (US)
Pages (from-to)274-279
Number of pages6
JournalSynapse
Volume23
Issue number4
DOIs
StatePublished - Aug 1 1996

Keywords

  • Hippocampus
  • Limbic system
  • Phencyclidine
  • Psychosis
  • Receptor binding
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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