Regional and temporal differential regulation of the N-methyl-D-aspartate receptor by phencyclidine during development



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Disruptions in glutamatergic neurotransmission may play a role in the pathogenesis of schizophrenia. The purpose of this study was to determine phencyclidine (PCP)-induced changes in the NMDA receptor subunit composition and the relationship of these changes to the deficits in pre-pulse inhibition (PPI) caused by PCP treatment. Postnatal rats were treated with atypical or typical antipsychotics or selective dopamine or serotonin receptor antagonists prior to acute or sub-chronic PCP. This study provides evidence that two distinct mechanisms underlie effects of acute and sub-chronic PCP on NMDA receptor subunit up-regulation. Furthermore, we discovered that D1, D2, and 5-HT2A receptors play a pivotal role in sub-chronic PCP-induced up-regulation of NR1 and NR2A. Finally, we were able to correlate changes in NMDA receptor subunits to the behavioral effects of PCP in this animal model of schizophrenia.



schizophrenia, olanzapine, animal model