Department of Psychology, California State University, San Bernardino, San Bernardino, CA, 92407, United States.
Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, United States.
Alcohol. 2020 Nov;88:65-72. doi: 10.1016/j.alcohol.2020.06.003. Epub 2020 Jun 30.
Adolescence is a time of marked changes in sleep, neuromaturation, and alcohol use. While there is substantial evidence that alcohol disrupts sleep and that disrupted sleep may play a role in the development of alcohol use disorders (AUD), there is very little known about the brain mechanisms underlying this phenomenon. The orexin (also known as hypocretin) system is fundamental for a number of homeostatic mechanisms, including the initiation and maintenance of wakefulness that may be impacted by adolescent alcohol exposure. The current study investigated the impact of adolescent ethanol exposure on adult orexin-A/hypocretin-1 immunoreactive (orexin-A + IR) cells in hypothalamic nuclei in two models of adolescent intermittent ethanol (AIE) exposure. Both models assess adult hypothalamic orexin following either an AIE vapor exposure paradigm, or an AIE intragastric gavage paradigm during adolescence. Both AIE exposure models found that binge levels of ethanol intoxication during adolescence significantly increased adult orexin-A + IR expression in the anterior hypothalamic nucleus (AHN). Further, both AIE models found no change in orexin-A + IR in the posterior hypothalamic area (PH), perifornical nucleus (PeF), dorsomedial hypothalamic nucleus dorsal part (DMD) or lateral hypothalamic area (LH). However, AIE vapor exposure reduced orexin-A + IR in the paraventricular nucleus (PVN), but AIE gavage exposure did not. These findings suggest that the AHN orexinergic system is increased in adults following binge-like patterns of intoxication during adolescence. Altered adult AHN orexin could contribute to long-lasting changes in sleep.
青春期是睡眠、神经成熟和酒精使用显著变化的时期。虽然有大量证据表明酒精会干扰睡眠，而睡眠中断可能在酒精使用障碍（AUD）的发展中起作用，但对于这一现象的大脑机制知之甚少。食欲素（也称为下丘脑泌素）系统对于许多体内平衡机制至关重要，包括觉醒的开始和维持，而青春期酒精暴露可能会影响这些机制。目前的研究调查了青春期乙醇暴露对两种青春期间歇性乙醇（AIE）暴露模型中成年下丘脑核食欲素-A/下丘脑泌素-1 免疫反应性（orexin-A + IR）细胞的影响。这两种模型都评估了成年下丘脑食欲素，要么是通过 AIE 蒸气暴露范式，要么是通过青春期时的 AIE 灌胃方案。两种 AIE 暴露模型都发现，青春期 binge 水平的乙醇中毒会显著增加成年前下丘脑核（AHN）中的 orexin-A + IR 表达。此外，两种 AIE 模型均未发现下丘脑后区（PH）、穹隆周核（PeF）、下丘脑背内侧核背侧部（DMD）或下丘脑外侧区（LH）中的 orexin-A + IR 发生变化。然而，AIE 蒸气暴露会减少室旁核（PVN）中的 orexin-A + IR，但 AIE 灌胃暴露不会。这些发现表明，在青春期 binge 样中毒模式后，成年 AHN 食欲素能系统增加。成年 AHN 食欲素的改变可能导致睡眠的持久变化。
