Subchronic Administration of Phencyclidine Produces Hypermethylation in the Parvalbumin Gene Promoter in Rat Brain

Abstract

AIM: 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. MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSION: Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis.