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Updated: Jun 3, 2026

Chronic Social Defeat Stress in Early Adolescent Male Mice
Published on: January 24, 2025
Early life stress disrupts peripubertal development of aggression in male mice
Mumeko C Tsuda1, Naoko Yamaguchi, Sonoko Ogawa
1Laboratory of Behavioral Neuroendocrinology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Abstract:
To investigate the effects of early life stress on the development of social behaviors in male mice, we examined behavioral responses toward same sex stimulus mice in the social investigation test and aggressive behaviors in peripubertal male mice exposed to maternal separation (MS) during the first 2 weeks of life. MS suppressed aggressive behaviors from 5-9 weeks of age, but had no effect on social investigative behaviors in the social investigation test. Investigation of neuroendocrine bases of behavioral effects of MS showed that MS reduced plasma testosterone levels and decreased arginine vasopressin and increased oxytocin immunoreactivity in the paraventricular nucleus of peripubertal males. These results collectively suggest that early life stress disrupts the development of male aggressive behaviors and associated neuroendocrine systems.
Insights
Early life stress, through maternal separation (MS), suppressed aggressive behaviors in male mice. This stress also altered key neuroendocrine systems, impacting testosterone and neuropeptide levels.
Area of Science:
- Neuroscience
- Behavioral Biology
- Endocrinology
Background:
- Early life stress (ELS) is a significant environmental factor impacting neurodevelopment.
- The effects of ELS on social behavior and neuroendocrine function in males require further elucidation.
Purpose of the Study:
- To investigate the impact of maternal separation (MS) on social and aggressive behaviors in male mice.
- To explore the neuroendocrine mechanisms underlying behavioral changes induced by MS.
Main Methods:
- Male mice underwent maternal separation (MS) during the first two weeks of life.
- Behavioral assessments included the social investigation test and aggressive behavior tests.
- Neuroendocrine analysis involved measuring plasma testosterone and brain neuropeptide (arginine vasopressin, oxytocin) levels.
Main Results:
- MS significantly suppressed aggressive behaviors in male mice from 5 to 9 weeks of age.
- No significant effects of MS were observed on social investigative behaviors.
- MS led to reduced plasma testosterone levels and altered arginine vasopressin and oxytocin immunoreactivity in the paraventricular nucleus.
Conclusions:
- Early life stress disrupts the development of male aggressive behaviors.
- MS affects neuroendocrine systems, including testosterone and neuropeptide regulation.
- These findings highlight the long-term consequences of early stress on social behavior and neurobiology.

