Yeoh Jiann Wei, Campbell Erin J, James Morgan H, Graham Brett A, Dayas Christopher V
Neurobiology of Addiction Laboratory, The Centre for Translational Neuroscience and Mental Health Research, School of Biomedical Sciences and Pharmacy, University of Newcastle and the Hunter Medical Research Institute Newcastle, NSW, Australia.
Front Neurosci. 2014 Feb 25;8:36. doi: 10.3389/fnins.2014.00036. eCollection 2014.
The tight regulation of sleep/wake states is critical for mental and physiological wellbeing. For example, dysregulation of sleep/wake systems predisposes individuals to metabolic disorders such as obesity and psychiatric problems, including depression. Contributing to this understanding, the last decade has seen significant advances in our appreciation of the complex interactions between brain systems that control the transition between sleep and wake states. Pivotal to our increased understanding of this pathway was the description of a group of neurons in the lateral hypothalamus (LH) that express the neuropeptides orexin A and B (hypocretin, Hcrt-1 and Hcrt-2). Orexin neurons were quickly placed at center stage with the demonstration that loss of normal orexin function is associated with the development of narcolepsy-a condition in which sufferers fail to maintain normal levels of daytime wakefulness. Since these initial seminal findings, much progress has been made in our understanding of the physiology and function of the orexin system. For example, the orexin system has been identified as a key modulator of autonomic and neuroendocrine function, arousal, reward and attention. Notably, studies in animals suggest that dysregulation of orexin function is associated with neuropsychiatric states such as addiction and mood disorders including depression and anxiety. This review discusses the progress associated with therapeutic attempts to restore orexin system function and treat neuropsychiatric conditions such as addiction, depression and anxiety. We also highlight potential pitfalls and challenges associated with targeting this system to treat these neuropsychiatric states.
睡眠/觉醒状态的严格调控对心理和生理健康至关重要。例如，睡眠/觉醒系统失调会使个体易患肥胖等代谢紊乱疾病以及包括抑郁症在内的精神问题。在这一认识过程中，过去十年里我们对控制睡眠与觉醒状态转换的脑系统之间复杂相互作用的理解取得了重大进展。对这一通路认识的加深，关键在于对下丘脑外侧区（LH）中一组表达神经肽食欲素A和B（下丘脑泌素，Hcrt-1和Hcrt-2）的神经元的描述。随着正常食欲素功能丧失与发作性睡病的发生相关联这一发现的证实，食欲素神经元迅速成为研究焦点——发作性睡病患者无法维持正常的日间清醒水平。自这些最初的开创性发现以来，我们对食欲素系统的生理和功能有了更多了解。例如，食欲素系统已被确定为自主神经和神经内分泌功能、觉醒状态、奖赏和注意力的关键调节因子。值得注意的是，动物研究表明，食欲素功能失调与成瘾等神经精神状态以及包括抑郁症和焦虑症在内的情绪障碍有关。本综述讨论了恢复食欲素系统功能及治疗成瘾、抑郁症和焦虑症等神经精神疾病的治疗尝试所取得的进展。我们还强调了针对该系统治疗这些神经精神状态时潜在的陷阱和挑战。
