Phencyclidine produces changes in NMDA and kainate receptor binding in rat hippocampus over a 48-hour time course.
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 CA1 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.
Gao
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Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore 21228, USA.
Tamminga
C A
CA
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D010622:Phencyclidine; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate