pISSN 1226-4512 eISSN 2093-3827


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Original Article

Korean J Physiol Pharmacol 2019; 23(6): 467-474

Published online November 1, 2019 https://doi.org/10.4196/kjpp.2019.23.6.467

Copyright © Korean J Physiol Pharmacol.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead

Hwayoung Lee1, Minyoung Lee1, Hyung-Ki Kim1, Young Ock Kim2, Jun-Tack Kwon1, and Hak-Jae Kim1,*

1Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan 31151, 2Department of Bio-Environmental Chemistry, College of Agriculture and Life Sciences, Chungnam National University, Daejeon 34134, Korea

Correspondence to:Hak-Jae Kim
E-mail: hak3962@sch.ac.kr

Received: March 30, 2019; Revised: August 26, 2019; Accepted: October 8, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Keywords: Animal model, Behavior rating scale, Clozapine, Lead poisoning, Neurodevelopmental disorder