Rats given phencyclidine (PCP) for 7 days showed increased DNA methylation at one of two specific sites in the parvalbumin gene promoter in both the prefrontal cortex and hippocampus six weeks later, compared to rats given a vehicle. No change was seen in a global measure of DNA methylation. This hypermethylation may contribute to parvalbumin neuron deficits in this animal model of psychosis, which are also observed in schizophrenia.
Sub-chronic exposure to the NMDA receptor antagonist phencyclidine (PCP) in rats produced localized reductions in grey matter density in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala, along with reduced cortical thickness in the insular cortex. PCP-treated rats also showed impaired sustained visual attention on a 5-choice serial reaction time task, especially under higher attentional load, but no significant effect on attentional filtering in an acoustic startle paradigm. These findings indicate that NMDA receptor antagonism can cause brain structural abnormalities in regions implicated in schizophrenia and dissociable attentional deficits.