Sleep restriction during opioid abstinence affects the hypothalamic-pituitary-adrenal (HPA) axis in male and female rats. 2023

Hershel Raff, and Breanna L Glaeser, and Aniko Szabo, and Christopher M Olsen, and Carol A Everson
Department of Medicine (Endocrinology and Molecular Medicine), Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.

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.

UI MeSH Term Description Entries
D007030 Hypothalamo-Hypophyseal System A collection of NEURONS, tracts of NERVE FIBERS, endocrine tissue, and blood vessels in the HYPOTHALAMUS and the PITUITARY GLAND. This hypothalamo-hypophyseal portal circulation provides the mechanism for hypothalamic neuroendocrine (HYPOTHALAMIC HORMONES) regulation of pituitary function and the release of various PITUITARY HORMONES into the systemic circulation to maintain HOMEOSTASIS. Hypothalamic Hypophyseal System,Hypothalamo-Pituitary-Adrenal Axis,Hypophyseal Portal System,Hypothalamic-Pituitary Unit,Hypothalamic Hypophyseal Systems,Hypothalamic Pituitary Unit,Hypothalamo Hypophyseal System,Hypothalamo Pituitary Adrenal Axis,Portal System, Hypophyseal
D008297 Male Males
D010913 Pituitary-Adrenal System The interactions between the anterior pituitary and adrenal glands, in which corticotropin (ACTH) stimulates the adrenal cortex and adrenal cortical hormones suppress the production of corticotropin by the anterior pituitary. Pituitary Adrenal System,Pituitary-Adrenal Systems,System, Pituitary-Adrenal,Systems, Pituitary-Adrenal
D003345 Corticosterone An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
D000324 Adrenocorticotropic Hormone An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP). ACTH,Adrenocorticotropin,Corticotropin,1-39 ACTH,ACTH (1-39),Adrenocorticotrophic Hormone,Corticotrophin,Corticotrophin (1-39),Corticotropin (1-39),Hormone, Adrenocorticotrophic,Hormone, Adrenocorticotropic
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012890 Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Sleep Habits,Sleeping Habit,Sleeping Habits,Habit, Sleep,Habit, Sleeping,Habits, Sleep,Habits, Sleeping,Sleep Habit
D013315 Stress, Psychological Stress wherein emotional factors predominate. Cumulative Stress, Psychological,Emotional Stress,Individual Stressors,Life Stress,Psychological Cumulative Stress,Psychological Stress Experience,Psychological Stress Overload,Psychologically Stressful Conditions,Stress Experience, Psychological,Stress Measurement, Psychological,Stress Overload, Psychological,Stress Processes, Psychological,Stress, Emotional,Stressful Conditions, Psychological,Psychological Stress,Stress, Psychologic,Stressor, Psychological,Condition, Psychological Stressful,Condition, Psychologically Stressful,Conditions, Psychologically Stressful,Cumulative Stresses, Psychological,Experience, Psychological Stress,Individual Stressor,Life Stresses,Measurement, Psychological Stress,Overload, Psychological Stress,Psychologic Stress,Psychological Cumulative Stresses,Psychological Stress Experiences,Psychological Stress Measurement,Psychological Stress Measurements,Psychological Stress Overloads,Psychological Stress Processe,Psychological Stress Processes,Psychological Stresses,Psychological Stressful Condition,Psychological Stressful Conditions,Psychological Stressor,Psychological Stressors,Psychologically Stressful Condition,Stress Experiences, Psychological,Stress Processe, Psychological,Stress, Life,Stress, Psychological Cumulative,Stressful Condition, Psychological,Stressful Condition, Psychologically,Stressor, Individual
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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