Involvement of N-methyl-D-aspartate receptor GluN2C/GluN2D subunits in social behavior impairments in mice exposed to social defeat stress as juveniles.
Mikio Yoshida, Hikari Katada, Yuya Isozumi, Chiharu Suzuki, Akira Yoshimi, Norio Ozaki, Yukihiro Noda
Journal of Pharmacological Sciences March 1, 2025 DOI: 10.1016/j.jphs.2024.12.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice exposed to juvenile social defeat stress |
| Interventions | PPDA ketamine CIQ |
| Topics | Ketamine |
| Keywords | Glun2c/glun2d-containing nmda receptor Social behavior impairment Mental health Social stress bullying Peer pressure Social defeat Victimization Nmda receptor targeting Neuroscience brain receptors |
| Citations | 4 |
| Key findings | Elevated GluN2C and GluN2D proteins in the prefrontal cortex of stressed mice and the attenuation of social behavior impairments by PPDA and ketamine suggest that activation of these NMDA receptor subunits contributes to social behavior deficits from juvenile social defeat stress. |
Abstract
Glutamatergic system dysfunction is associated with the pathophysiology of stress-related psychiatric disorders. However, the role of N-methyl-D-aspartate (NMDA) receptor GluN2C and GluN2D subunits in the pathophysiology of adverse juvenile experiences remain unclear. This study aimed to investigate the involvement of GluN2C and GluN2D subunits in social behavior impairments in mice exposed to social defeat stress as juveniles. Acute administration of PPDA, a GluN2C/GluN2D antagonist, and ketamine, a non-competitive NMDA receptor antagonist, attenuated social behavior impairments in stressed mice. This attenuating effect of ketamine was partially inhibited by the administration of CIQ, a GluN2C/GluN2D-containing NMDA potentiator. The prefrontal cortex of stressed mice exhibited significantly elevated levels of GluN2C and GluN2D proteins compared to control mice. These findings suggest that activation of GluN2C- and/or GluN2D-containing NMDA receptors contributes to the development of social behavioral impairments induced by juvenile social defeat stress. Moreover, these subunits may play a role in the therapeutic effects of ketamine. Targeting GluN2C/GluN2D subunits of NMDA receptors may be novel therapeutic strategies for stress-related psychiatric disorders in adolescents with adverse juvenile experiences.