Sleep restriction during opioid abstinence affects the hypothalamic-pituitary-adrenal (HPA) axis in male and female rats

Authors

Hershel Raff, Advocate Aurora Health
Breanna L. Glaeser, Department of Pharmacology & Toxicology and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Aniko Szabo, Division of Biostatistics, Institute for Health & Equity, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Christopher M. Olsen, Departments of Pharmacology & Toxicology and Neurosurgery, Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Carol A. Everson, Department of Medicine (Endocrinology and Molecular Medicine) and Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Recommended Citation

Raff H, Glaeser BL, Szabo A, Olsen CM, Everson CA. Sleep restriction during opioid abstinence affects the hypothalamic-pituitary-adrenal (HPA) axis in male and female rats. Stress. 2023;26(1):2185864. doi:10.1080/10253890.2023.2185864

Affiliations

Aurora St. Luke's Medical Center

Abstract

Hypothalamic-pituitary-adrenal (HPA) axis dynamics are disrupted by opioids and may be involved in substance abuse; this persists during withdrawal and abstinence and is associated with co-morbid sleep disruption leading to vulnerability to relapse. We hypothesized that chronic sleep restriction (SR) alters the HPA axis diurnal rhythm and the sexually dimorphic response to acute stressor during opioid abstinence. We developed a rat model to evaluate the effect of persistent sleep loss during opioid abstinence on HPA axis dynamics in male and female rats. Plasma ACTH and corticosterone were measured diurnally and in response to acute restraint stress in rats Before (control) compared to During subsequent opioid abstinence without or with SR. Abstinence, regardless of sleep state, led to an increase in plasma ACTH and corticosterone in the morning in males. There was a tendency for higher PM plasma ACTH during abstinence in SR males (P = 0.076). ACTH and corticosterone responses to restraint were reduced in male SR rats whereas there was a failure to achieve the post-restraint nadir in female SR rats. There was no effect of the treatments or interventions on adrenal weight normalized to body weight. SR resulted in a dramatic increase in hypothalamic PVN AVP mRNA and plasma copeptin in male but not female rats. This corresponded to the attenuation of the HPA axis stress response in SR males during opioid abstinence. We have identified a potentially unique, sexually dimorphic role for magnocellular vasopressin in the control of the HPA axis during opioid abstinence and sleep restriction.

Document Type

Article

PubMed ID

36856367