Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2021.133
Autism-Like Behavioral Phenotypes in Mice Treated with Systemic N-Methyl-D-Aspartate
Keremkleroo Jym Adil, Edson Luck Gonzales, Chilly Gay Remonde, Kyung-Jun Boo, Se Jin Jeon* and Chan Young Shin*
School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul 05029, Republic of Korea
*E-mail: sjinjeon@kku.ac.kr (Jeon SJ), chanyshin@kku.ac.kr (Shin CY)
Tel: +82-2-454-5630 (Jeon SJ), +82-2-454-5630 (Shin CY)
Fax: +82-2-2030-7899 (Jeon SJ), +82-2-2030-7899 (Shin CY)
The first two authors contributed equally to this work.
Received: August 9, 2021; Revised: September 15, 2021; Accepted: September 17, 2021; Published online: October 27, 2021.
© 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
Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.


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