Prenatal Phencyclidine Treatment Induces Behavioral Deficits Through Impairment of GABAergic Interneurons in the Prefrontal Cortex

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2016 Apr 21

PMID 27095448

Citations 11

Authors

Kazuya Toriumi

Mika Oki

Eriko Muto

Junko Tanaka

Akihiro Mouri

Takayoshi Mamiya

Hyoung-Chun Kim

Toshitaka Nabeshima

Affiliations

Soon will be listed here.

Abstract

Rationale: We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons.

Objectives: We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC.

Methods: PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood.

Results: The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen.

Conclusions: These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.

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