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Rationale <p>Chronic stress is a major precipitating factor for mood disorders, which are diagnosed twice as frequently in women as in men. However, most preclinical models of chronic social defeat stress have limited use in females due to reduced aggression toward female intruders. The chronic non-discriminatory social defeat stress (CNSDS) model addresses these limitations by enabling the study of stress susceptibility across sexes in a variety of behavioral tasks including avoidance and simple reward behaviors. However, the effect of CNSDS susceptibility on complex reward behaviors has yet to be studied.</p> Objectives <p>Building on previous work validating CNSDS in both sexes, we aimed to refine the protocol for identifying CD-1 aggressors for CNSDS, optimize criteria for classifying susceptibility and resilience to stress, and assess how stress susceptibility affects complex reward behavior.</p> Methods <p>We evaluated aggression through attack frequency and submissive posture during CD-1 aggressor screening and CNSDS sessions to establish screening parameters. Following CNSDS exposure, male and female intruder mice were tested in an operant satiety-based outcome devaluation task.</p> Results <p>We observed that despite receiving fewer attacks, female mice are equally susceptible to CNSDS as males. CNSDS abolished satiety-based outcome devaluation, regardless of sex, in susceptible mice, but not in resilient mice.</p> Conclusions <p>These data suggest that CNSDS-defined stress phenotypes are behaviorally relevant across sexes and extend to deficits in complex reward behaviors, supporting CNSDS as a valuable model for studying sex-specific stress outcomes in mood disorders.</p>

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Male and female mice are similarly susceptible to chronic nondiscriminatory social defeat stress despite differences in attack frequency from aggressor

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月12日

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  • Allyson Bazer,
  • Katherine Denney,
  • Maria Chacona,
  • Catherine Montgomery,
  • Shriya Vinod,
  • Urboshi Datta,
  • Benjamin Adam Samuels

摘要

Rationale

Chronic stress is a major precipitating factor for mood disorders, which are diagnosed twice as frequently in women as in men. However, most preclinical models of chronic social defeat stress have limited use in females due to reduced aggression toward female intruders. The chronic non-discriminatory social defeat stress (CNSDS) model addresses these limitations by enabling the study of stress susceptibility across sexes in a variety of behavioral tasks including avoidance and simple reward behaviors. However, the effect of CNSDS susceptibility on complex reward behaviors has yet to be studied.

Objectives

Building on previous work validating CNSDS in both sexes, we aimed to refine the protocol for identifying CD-1 aggressors for CNSDS, optimize criteria for classifying susceptibility and resilience to stress, and assess how stress susceptibility affects complex reward behavior.

Methods

We evaluated aggression through attack frequency and submissive posture during CD-1 aggressor screening and CNSDS sessions to establish screening parameters. Following CNSDS exposure, male and female intruder mice were tested in an operant satiety-based outcome devaluation task.

Results

We observed that despite receiving fewer attacks, female mice are equally susceptible to CNSDS as males. CNSDS abolished satiety-based outcome devaluation, regardless of sex, in susceptible mice, but not in resilient mice.

Conclusions

These data suggest that CNSDS-defined stress phenotypes are behaviorally relevant across sexes and extend to deficits in complex reward behaviors, supporting CNSDS as a valuable model for studying sex-specific stress outcomes in mood disorders.