Social isolation alters hypothalamic pituitary adrenal axis activity after chronic variable stress in male C57BL/6 mice

Ashley L. Heck, Julietta A. Sheng, Alex M. Miller, Sally A. Stover, Natalie J. Bales, Sarah M.L. Tan, Renata M. Daniels, Theodore K. Fleury, Robert J. Handa

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The chronic variable stress (CVS) paradigm is frequently used to model the changes in hypothalamic pituitary adrenal (HPA) axis function characteristic of many stress-related diseases. However, male C57BL/6 mice are typically resistant to CVS’s effects, making it difficult to determine how chronic stress exposure may alter acute HPA function and regulation in these mice. As social support in rodents can profoundly influence physiological and behavioral processes, including the HPA axis, we sought to characterize the effects of CVS exposure on basal and acute stress-induced HPA axis function in pair- and single-housed adult male mice. Despite all subjects exhibiting decreased body weight gain after six weeks of CVS, the corticosterone response to a novel, acute restraint stressor was enhanced by CVS exclusively in single-housed males. CVS also significantly increased arginine vasopressin (AVP) mRNA in the hypothalamic paraventricular nucleus (PVN) in single-housed males only. Moreover, in single-, but not pair-housed mice, CVS attenuated decreases in circulating OT found following acute restraint. Only the effect of CVS to elevate PVN corticotropin releasing hormone (CRH) mRNA levels after an acute stressor was restricted to pair-housed mice. Collectively, our findings suggest that social isolation reveals effects of CVS on the HPA axis in male C57BL/6 mice.

Original languageEnglish (US)
Pages (from-to)457-465
Number of pages9
Issue number4
StatePublished - Jul 3 2020


  • Chronic variable stress (CVS)
  • corticotropin releasing hormone (CRH)
  • oxytocin (OT)
  • paraventricular nucleus (PVN)
  • social environment
  • vasopressin (AVP)

ASJC Scopus subject areas

  • Physiology
  • Neuropsychology and Physiological Psychology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Behavioral Neuroscience


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