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Vulnerability and resilience to activity-based anorexia are not sex-dependent

AI Summary
  • No sex differences in ABA susceptibility; male and female C57BL/6N mice show equivalent proportions of vulnerable and resilient phenotypes.
  • Vulnerable mice of both sexes develop catastrophic weight loss linked to excessive light cycle running, while resilient mice stabilise weight via adaptive consumption.
  • When food is available, vulnerable mice do not run more than resilient mice, so vulnerability is not due to choosing running over eating.
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Front Psychiatry. 2026 Oct 2;17:1897501. doi: 10.3389/fpsyt.2026.1897501. eCollection 2026.

ABSTRACT

INTRODUCTION: Anorexia nervosa (AN) is more prevalent in women than men, although rates in men are rising. Animal models can provide insight into whether this differential prevalence is rooted in biological mechanisms, but prior studies have yielded conflicting findings. Using the activity-based anorexia (ABA) model, we previously demonstrated that female mice exhibit distinct vulnerable and resilient phenotypes. Here, we use this phenotypic framework to investigate sex differences in ABA susceptibility.

METHODS: We tested young adult male C57BL/6N mice using the same ABA protocol used to test age-matched C57BL/6N females. Individual differences in daily bodyweight, food intake, water intake, and wheel running were analyzed and compared across sexes.

RESULTS: Males exhibit the same vulnerable and resilient phenotypes as females, with no sex difference in the proportion of mice exhibiting each phenotype or the repertoire of behaviors characterizing them. In both sexes, vulnerable mice exhibit catastrophic weight loss that is associated with excessive light cycle running, while resilient mice exhibit weight stabilization that is associated with adaptive changes in consumption. When food is available, vulnerable mice do not run more than resilient mice, indicating that vulnerability is not characterized by a decision to run instead of eat in either sex.

CONCLUSIONS: Our findings indicate that there are no sex differences in ABA in C57BL/6N mice. The shared behavioral responses to starvation observed across sexes demonstrate that ABA can be used to model adaptive and maladaptive responses to food restriction in men and women.

PMID:42890939 | PMC:PMC13672643 | DOI:10.3389/fpsyt.2026.1897501

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