The Scripps Research Institute, Molecular and Integrative Neurosciences Department, SP30-2120, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Brain Res. 2010 Feb 16;1314:145-61. doi: 10.1016/j.brainres.2009.12.027. Epub 2009 Dec 21.
Stress-like symptoms are an integral part of acute and protracted drug withdrawal, and several lines of evidence have shown that dysregulation of brain stress systems, including the extrahypothalamic corticotropin-releasing factor (CRF) system, following long-term drug use is of major importance in maintaining drug and alcohol addiction. Recently, two other neuropeptide systems have attracted interest, the nociceptin/orphanin FQ (N/OFQ) and orexin/hypocretin (Orx/Hcrt) systems. N/OFQ participates in a wide range of physiological responses, and the hypothalamic Orx/Hcrt system helps regulate several physiological processes, including feeding, energy metabolism, and arousal. Moreover, these two systems have been suggested to participate in psychiatric disorders, including anxiety and drug addiction. Dysregulation of these systems by chronic drug exposure has been hypothesized to play a role in the maintenance of addiction and dependence. Recent evidence demonstrated that interactions between CRF-N/OFQ and CRF-Orx/Hcrt systems may be functionally relevant for the control of stress-related addictive behavior. The present review discusses recent findings that support the hypotheses of the participation and dysregulation of these systems in drug addiction and evaluates the current understanding of interactions among these stress-regulatory peptides.
应激样症状是急性和慢性药物戒断的一个组成部分，有几条证据表明，长期使用药物后大脑应激系统（包括下丘脑以外的促肾上腺皮质激素释放因子（CRF）系统）的失调对于维持药物和酒精成瘾非常重要。最近，另外两个神经肽系统引起了人们的兴趣，即孤啡肽/孤啡肽（N/OFQ）和食欲素/下丘脑分泌素（Orx/Hcrt）系统。N/OFQ 参与了广泛的生理反应，而下丘脑的 Orx/Hcrt 系统有助于调节包括进食、能量代谢和觉醒在内的多种生理过程。此外，这两个系统被认为参与了包括焦虑和药物成瘾在内的精神疾病。慢性药物暴露导致这些系统的失调被假设在成瘾和依赖的维持中发挥作用。最近的证据表明，CRF-N/OFQ 和 CRF-Orx/Hcrt 系统之间的相互作用可能与控制应激相关的成瘾行为具有功能相关性。本文综述了支持这些系统参与药物成瘾和失调的假设，并评估了目前对这些应激调节肽相互作用的理解。
