The effects of chronic sleep restriction on the hypothalamic-pituitary-adrenal axis and its interaction with abstinence from opioid use

Abstract Study objectives The hypothalamic-pituitary-adrenal (HPA) axis is critical in regulating responses to physiological and psychological disturbances. Chronic sleep restriction (SR) interacts with the HPA axis in ways that are poorly delineated. The present study evaluated how chronic SR alters pituitary and adrenal function. Chronic SR was studied both alone and in a model of opioid use disorder as a potential cause of HPA axis abnormalities during abstinence. Methods After established self-administration of oxycodone or a saline control, male and female rats were either chronically sleep restricted or allowed to sleep ad libitum for five weeks to permit changes in phenotype to manifest. Tests of pituitary and adrenal function were then carried out using acute CRH and dexamethasone-ACTH stimulation testing. Results Sexual dimorphisms were prominent in the effects of chronic SR on the HPA axis which did not vary by prior opioid exposure. There were essentially no abnormalities in the HPA axis that were due to prior opioid exposure alone. In male SR rats, basal corticosterone concentrations decreased, ACTH responses to stimulation were enhanced, and ACTH suppression by dexamethasone was reduced. In female SR rats, the corticosterone response to CRH-stimulated ACTH release peaked early. Both male and female SR rats consumed more food relative to body weight than comparison rats, indicating homeostatic disruption that is known to require HPA axis mediation. Conclusions Chronic SR interferes with HPA axis dynamics in sexually dimorphic ways that are expected to differentially affect SR-induced pathophysiology and disease risks. Chronic SR caused the HPA axis abnormalities observed during abstinence, providing biological linkage between two hypothesized risk factors in vulnerability to drug taking and relapse that demonstrate sexual dimorphisms.