James Morgan H, Campbell Erin J, Dayas Christopher V
Brain Health Institute, Rutgers University/Rutgers Biomedical and Health Sciences, Piscataway, NJ, USA.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 2337, Australia.
Curr Top Behav Neurosci. 2017;33:197-219. doi: 10.1007/7854_2016_56.
Orexins (hypocretins) are critically involved in coordinating appropriate physiological and behavioral responses to aversive and threatening stimuli. Acute stressors engage orexin neurons via direct projections from stress-sensitive brain regions. Orexin neurons, in turn, facilitate adaptive behavior via reciprocal connections as well as via direct projections to the hypophysiotropic neurons that coordinate the hypothalamic-pituitary-adrenal (HPA) axis response to stress. Consequently, hyperactivity of the orexin system is associated with increased motivated arousal and anxiety, and is emerging as a key feature of panic disorder. Accordingly, there has been significant interest in the therapeutic potential of pharmacological agents that antagonize orexin signaling at their receptors for the treatment of anxiety disorders. In contrast, disorders characterized by inappropriately low levels of motivated arousal, such as depression, generally appear to be associated with hypoactivity of the orexin system. This includes narcolepsy with cataplexy, a disorder characterized by the progressive loss of orexin neurons and increased rates of moderate/severe depression symptomology. Here, we provide a comprehensive overview of both clinical and preclinical evidence highlighting the role of orexin signaling in stress reactivity, as well as how perturbations to this system can result in dysregulated behavioral phenotypes.
食欲素（下丘脑泌素）在协调对厌恶和威胁性刺激的适当生理和行为反应中起着关键作用。急性应激源通过来自应激敏感脑区的直接投射激活食欲素神经元。反过来，食欲素神经元通过相互连接以及通过直接投射到协调下丘脑 - 垂体 - 肾上腺（HPA）轴对应激反应的促垂体神经元来促进适应性行为。因此，食欲素系统的过度活跃与动机性觉醒和焦虑增加有关，并正在成为惊恐障碍的一个关键特征。相应地，人们对在其受体处拮抗食欲素信号传导的药物制剂治疗焦虑症的治疗潜力产生了浓厚兴趣。相比之下，以动机性觉醒水平过低为特征的疾病，如抑郁症，通常似乎与食欲素系统的活动不足有关。这包括发作性睡病伴猝倒，这是一种以食欲素神经元逐渐丧失和中度/重度抑郁症状发生率增加为特征的疾病。在这里，我们提供了临床和临床前证据的全面概述，突出了食欲素信号在应激反应性中的作用，以及该系统的扰动如何导致行为表型失调。
