An increase in NMDA-sensitive [ 3H]glutamate and [ 3H]kainate binding in hippocampus 24 hours after PCP

Abstract

Considerable research has identified a variety of acute PCP-induced biochemical changes in brain; but, little study has been devoted to characterizing delayed PCP-induced actions. These could potentially be associated with the prolonged psychotomimetic effects of the drug in humans. Here we studied delayed PCP-induced alterations in glutamate receptor subtype binding across a range of PCP doses, based on our previous findings of delayed regional cerebral metabolism changes with PCP. We report that 24 h after a single dose, PCP increases N- methyl- d - aspartate (NMDA)-sensitive [ 3H]glutamate binding in hippocampus (CA 1) in an apparent dose-sensitive manner; no other dose-sensitive regional changes in NMDA binding sites were apparent in a sampling of 19 brain regions. [ 3H]kainate binding sites were increased in CA 3 and dentate gyrus, but only at the high drug dose. Moreover, PCP appeared to have a general delayed effect in upregulating NMDA receptor binding in limbic-associated brain areas at its middle dose, and in upregulating [ 3H]kainate binding in neocortical and limbic area at its high dose. No PCP effects were noted on AMPA receptor binding. These delayed actions of PCP may be informative about the mechanism of PCP psychosis.