The effects of sleep restriction during abstinence on oxycodone seeking: Sex-dependent moderating effects of behavioral and hypothalamic-pituitary-adrenal axis-related phenotypes

Authors

Christopher M. Olsen, Departments of Pharmacology & Toxicology and Neurosurgery, Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address: colsen@mcw.edu.
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.
Hershel Raff, Advocate Aurora Health
Carol A. Everson, Department of Medicine (Endocrinology and Molecular Medicine) and Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Recommended Citation

Olsen CM, Glaeser BL, Szabo A, Raff H, Everson CA. The effects of sleep restriction during abstinence on oxycodone seeking: Sex-dependent moderating effects of behavioral and hypothalamic-pituitary-adrenal axis-related phenotypes. Physiol Behav. 2023;272:114372. doi:10.1016/j.physbeh.2023.114372

Affiliations

Aurora St. Luke's Medical Center

Abstract

During opioid use and abstinence, sleep disturbances are common and are thought to exacerbate drug craving. In this study, we tested the hypothesis that sleep restriction during abstinence from oxycodone self-administration would increase drug seeking during extinction and footshock reinstatement tests. We also performed behavioral phenotyping to determine if individual variation in responses to stressors and/or pain are associated with oxycodone seeking during abstinence, as stress, pain and sleep disturbance are often co-occurring phenomena. Sleep restriction during abstinence did not have selective effects on oxycodone seeking for either sex in extinction and footshock reinstatement tests. Some phenotypes were associated with drug seeking; these associations differed by sex and type of drug seeking assessment. In female rats, pain-related phenotypes were related to high levels of drug seeking during the initial extinction session. In male rats, lower anxiety-like behavior in the open field was associated with greater drug seeking, although this effect was lost when correcting for oxycodone intake. Adrenal sensitivity prior to oxycodone exposure was positively associated with footshock reinstatement in females. This work identifies sex-dependent relationships between HPA axis function and opioid seeking, indicating that HPA axis function could be a therapeutic target for the treatment of opioid use disorder, with tailored approaches based on sex. Sleep disturbance during abstinence did not appear to be a major contributing factor to opioid seeking.

Document Type

Article

PubMed ID

37805135