Department of Medicine (Endocrinology and Molecular Medicine), Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Advocate Aurora Research Institute, Milwaukee, WI, USA.
Stress. 2023 Jan;26(1):2185864. doi: 10.1080/10253890.2023.2185864.
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 ( = 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 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.
下丘脑-垂体-肾上腺 (HPA) 轴的活动被阿片类药物打乱，可能与物质滥用有关；这种情况在戒断和禁欲期间持续存在，并与共病性睡眠中断有关，导致易复发。我们假设慢性睡眠限制 (SR) 会改变 HPA 轴的昼夜节律和对阿片类药物戒断期间急性应激源的性别二态反应。我们开发了一种大鼠模型，以评估在阿片类药物戒断期间持续睡眠剥夺对雄性和雌性大鼠 HPA 轴动力学的影响。在大鼠中，与对照相比，在随后的阿片类药物戒断期间（无论是否有 SR），分别测量了血浆促肾上腺皮质激素 (ACTH) 和皮质酮的昼夜变化和对急性束缚应激的反应。无论睡眠状态如何，戒断都会导致雄性大鼠清晨血浆 ACTH 和皮质酮水平升高。SR 雄性大鼠在戒断期间 PM 时血浆 ACTH 升高的趋势（ = 0.076）。束缚应激时，雄性 SR 大鼠的 ACTH 和皮质酮反应降低，而雌性 SR 大鼠则未能达到应激后最低点。这些治疗或干预措施对体重标准化的肾上腺重量没有影响。SR 导致雄性大鼠下丘脑 AVP mRNA 和血浆 copeptin 显著增加，但雌性大鼠没有。这与阿片类药物戒断期间 SR 雄性大鼠 HPA 轴应激反应的减弱相对应。我们已经确定了在阿片类药物戒断和睡眠限制期间，大细胞加压素在 HPA 轴控制中具有潜在的独特性别二态作用。
