Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2021.194
Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development
Keremkleroo Jym Adil1,†, Chilly Gay Remonde1,†, Edson Luck Gonzales1, Kyung-Jun Boo1, Kyong Ja Kwon1, Dong Hyun Kim1, Hee Jin Kim2, Jae Hoon Cheong3, Chan Young Shin1,* and Se Jin Jeon1,*
1Department of Pharmacology, School of Medicine, Konkuk University, Seoul 05029,
2Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Seoul 01795,
3School of Pharmacy, Jeonbuk National University, Jeonju 54896, Republic of Korea
*E-mail: chanyshin@kku.ac.kr (Shin CY), sjinjeon@hanmail.net (Jeon SJ)
Tel: +82-2-454-5630 (Shin CY), +82-2-540-5630 (Jeon SJ)
Fax: +82-2-548-5630 (Shin CY), +82-2-548-5630 (Jeon SJ)
The first two authors contributed equally to this work.
Received: December 26, 2021; Revised: January 7, 2022; Accepted: January 11, 2022; Published online: February 7, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/ inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDAtreated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.
Keywords: Autism spectrum disorder, NMDA, Excitation/inhibition imbalance, Mouse model, Social deficit


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