Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain.

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.

Study at a glance

Abstract

A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation. PCP administration induced significantly greater methylation at one of two Pvalb CpG sites in both prefrontal cortex and hippocampus, while no significant difference was found in long interspersed nucleotide element-1, a global measure of DNA methylation. Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis.