Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, 65201, United States.
Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, 65201, United States.
Neurosci Lett. 2020 Nov 20;739:135347. doi: 10.1016/j.neulet.2020.135347. Epub 2020 Oct 1.
Alcohol use disorders (AUD) are chronic relapsing brain disorder characterized by compulsive and heavy alcohol consumption. During acute withdrawal, patients with AUD display excessive daytime sleepiness, a condition linked to serious life-threatening complications, however, the mechanism is not known. Orexin and melanin-concentrating hormone (MCH) are the two hypothalamic neuropeptides that regulate many behaviors including sleep-wakefulness, and alcohol consumption, reinforcement, and reinstatement. Importantly, loss of orexin neurons causes narcolepsy, a severe sleep disorder with excessive daytime sleepiness. Does acute alcohol withdrawal reduce orexin gene expression? To investigate this, male Sprague-Dawley rats were divided in two groups: Rats were either administered with alcohol, mixed with infant formula (alcohol group) or control mixture containing water and infant formula (Controls) by gastric intubation every 8 h for 4 days using Majchrowicz's chronic binge drinking protocol. The doses of alcohol were adjusted depending on degree of intoxication, exhibited by animals, prior to each dose. The animals were euthanized after 12 h of last alcohol/water administration. During withdrawal, the hypothalamus was rapidly dissected out, and the expressions of orexin and MCH genes were examined by Real-time PCR. There was a significant reduction in orexin gene expression in rats subjected to alcohol withdrawal as compared to controls. No such change was observed in the MCH gene expression. These results suggest that downregulation of orexin gene expression may be a possible mechanism responsible for excessive daytime sleepiness associated with alcohol withdrawal in patients with AUD.
酒精使用障碍（AUD）是一种慢性复发性脑部疾病，其特征是强制性和大量饮酒。在急性戒断期间，AUD 患者表现出过度日间嗜睡，这与严重的危及生命的并发症有关，但机制尚不清楚。食欲素和黑色素浓缩激素（MCH）是两种下丘脑神经肽，可调节包括睡眠-觉醒在内的许多行为，以及酒精摄入、强化和复燃。重要的是，食欲素神经元的丧失会导致嗜睡症，这是一种严重的睡眠障碍，伴有过度日间嗜睡。急性酒精戒断是否会降低食欲素基因表达？为了研究这一点，雄性 Sprague-Dawley 大鼠分为两组：大鼠通过胃内灌胃每天每 8 小时接受酒精（与婴儿配方混合）或含有水和婴儿配方的对照混合物（对照组），连续 4 天，使用 Majchrowicz 的慢性狂欢性饮酒方案。根据动物在每次给药前的醉酒程度调整酒精剂量。最后一次酒精/水给药后 12 小时处死动物。在戒断期间，迅速取出下丘脑，并通过实时 PCR 检查食欲素和 MCH 基因的表达。与对照组相比，酒精戒断的大鼠食欲素基因表达显著降低。MCH 基因表达没有观察到这种变化。这些结果表明，食欲素基因表达的下调可能是 AUD 患者酒精戒断相关过度日间嗜睡的一个可能机制。
