Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Neuropharmacology. 2020 May 15;168:108013. doi: 10.1016/j.neuropharm.2020.108013. Epub 2020 Feb 15.
The neuropeptide hypocretin/orexin plays a broad and important role in physiological functions ranging from addiction, stress, and anxiety to sleep, energy metabolism, and homeostatic regulation. A number of recent reviews addressing the importance of orexin for different addictive behaviors, especially the contribution of orexin-1-receptors (Ox1Rs) in responding for intoxicants in higher-motivation individuals and situations, and orexin-2-receptor (Ox2Rs) in stress-related aspects of addictive responding. This may parallel the importance of more lateral orexin neurons in the hypothalamus for reward and more medial for stress and arousal. However, there is clearly also some crossover, which may reflect, in part, where positive and negative conditioning (reward- and relief-seeking) are both present concurrently in established addiction, and also where orexin signaling can differ in subregions of a particular brain region. Here, we attempt to examine and synthesize some of the most recent work addressing orexin functions in addiction, including a particular role for Ox1Rs for driving responding in higher-motivation individuals and under higher levels of effort. While there are some commonalities across addictive substances addressed here (alcohol, cocaine, opiates), there are also some differences, which may relate to several factors including the speed of intoxication with a given substance. Together, recent findings have shed important insight and clues into what a more unified role of Ox1Rs might entail, and critical areas for future work. In addition, these many studies support the development of Ox1R blockers for use in humans to counteract addiction and other disorders of motivation. This article is part of the special issue on Neuropeptides.
神经肽食欲素/下丘脑分泌素在生理功能中发挥着广泛而重要的作用，涉及成瘾、应激、焦虑、睡眠、能量代谢和体内平衡调节等多个方面。最近有许多综述文章探讨了食欲素在不同成瘾行为中的重要性，特别是食欲素-1 受体（Ox1Rs）在高动机个体和情境中对成瘾物质的反应，以及食欲素-2 受体（Ox2Rs）在成瘾反应的应激相关方面的作用。这可能与下丘脑外侧食欲素神经元在奖励方面更为重要，而内侧神经元在应激和觉醒方面更为重要有关。然而，也存在明显的重叠，这可能部分反映了在已确立的成瘾中，正性和负性条件作用（奖励寻求和缓解寻求）同时存在，以及食欲素信号在特定脑区的不同亚区可能存在差异。在这里，我们试图检查和综合一些最近关于食欲素在成瘾中的作用的研究，包括 Ox1Rs 在高动机个体和高努力水平下驱动反应的特定作用。虽然这里所涉及的成瘾物质（酒精、可卡因、阿片类药物）有一些共同之处，但也存在一些差异，这可能与许多因素有关，包括特定物质中毒的速度。总之，最近的研究结果为 Ox1Rs 的更统一作用提供了重要的见解和线索，并为未来的工作指明了关键领域。此外，这些研究支持开发 Ox1R 阻断剂用于人类，以对抗成瘾和其他动机障碍。本文是神经肽特刊的一部分。
