Drexel University College of Medicine, Philadelphia, PA, United States.
The Rockefeller University, New York, NY, United States.
Int Rev Neurobiol. 2017;136:199-237. doi: 10.1016/bs.irn.2017.06.006. Epub 2017 Aug 8.
The neuropeptide orexin/hypocretin (OX), while largely transcribed within the hypothalamus, is released throughout the brain to affect complex behaviors. Primarily through the hypothalamus itself, OX homeostatically regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, through extrahypothalamic limbic brain regions, OX promotes seeking and intake of rewarding substances of abuse, like palatable food, alcohol, nicotine, and cocaine. This neuropeptide, in turn, is stimulated by the intake of or early life exposure to these substances, forming a nonhomeostatic, positive feedback loop. The specific OX receptor involved in these behaviors, whether adaptive behavior or substance seeking and intake, is dependent on the particular brain region that contributes to them. Thus, we propose that, while the primary function of OX is to maintain arousal for the performance of adaptive behaviors, this neuropeptide system is readily co-opted by rewarding substances that involve positive feedback, ultimately promoting their abuse.
神经肽食欲素/下丘脑分泌素（OX）主要在下丘脑转录，但也会在整个大脑中释放，以影响复杂行为。主要通过下丘脑自身，OX 对生存所需的适应性行为进行同态调节，包括食物摄入、睡眠-觉醒调节、交配和母性行为。然而，通过下丘脑以外的边缘脑区域，OX 促进对奖赏性滥用物质的寻求和摄入，如美味食物、酒精、尼古丁和可卡因。反过来，这种神经肽会受到这些物质摄入或早期生活暴露的刺激，形成非同态正反馈循环。参与这些行为的特定 OX 受体，无论是适应性行为还是物质寻求和摄入，取决于对其有贡献的特定脑区。因此，我们提出，虽然 OX 的主要功能是维持觉醒以进行适应性行为，但这个神经肽系统很容易被涉及正反馈的奖赏性物质所利用，最终促进它们的滥用。
