Engel Jörgen A, Jerlhag Elisabet
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, POB 431, 405 30, Gothenburg, Sweden.
CNS Drugs. 2014 Oct;28(10):875-86. doi: 10.1007/s40263-014-0178-y.
Food intake and appetite are regulated by various circulating hormones including ghrelin and glucagon-like-peptide 1 (GLP-1). Ghrelin, mainly released from the stomach, increases food intake, induces appetite, enhances adiposity as well as releases growth hormone. Hypothalamic "ghrelin receptors" (GHS-R1A) have a critical role in food intake regulation, but GHS-R1A are also expressed in reward related areas. GLP-1 is produced in the intestinal mucosa as well as in the hindbrain in response to nutrient ingestion. This gut-brain hormone reduces food intake as well as regulates glucose homeostasis, foremost via GLP-1 receptors in hypothalamus and brain stem. However, GLP-1 receptors are expressed in areas intimately associated with reward regulation. Given that regulation of food and drug intake share common neurobiological substrates, the possibility that ghrelin and GLP-1 play an important role in reward regulation should be considered. Indeed, this leading article describes that the orexigenic peptide ghrelin activates the cholinergic-dopaminergic reward link, an important part of the reward systems in the brain associated with reinforcement and thereby increases the incentive salience for motivated behaviors via this system. We also review the role of ghrelin signaling for reward induced by alcohol and addictive drugs from a preclinical, clinical and human genetic perspective. In addition, the recent findings showing that GLP-1 controls reward induced by alcohol, amphetamine, cocaine and nicotine in rodents are overviewed herein. Finally, the role of several other appetite regulatory hormones for reward and addiction is briefly discussed. Collectively, these data suggest that ghrelin and GLP-1 receptors may be novel targets for development of pharmacological treatments of alcohol and drug dependence.
食物摄入和食欲受多种循环激素调节，包括胃饥饿素和胰高血糖素样肽1（GLP-1）。胃饥饿素主要由胃释放，可增加食物摄入量、诱导食欲、促进肥胖以及释放生长激素。下丘脑“胃饥饿素受体”（GHS-R1A）在食物摄入调节中起关键作用，但GHS-R1A也在与奖赏相关的区域表达。GLP-1在肠道黏膜以及后脑产生，以响应营养物质的摄入。这种肠-脑激素可减少食物摄入量并调节葡萄糖稳态，主要通过下丘脑和脑干中的GLP-1受体实现。然而，GLP-1受体也在与奖赏调节密切相关的区域表达。鉴于食物和药物摄入的调节共享共同的神经生物学底物，应考虑胃饥饿素和GLP-1在奖赏调节中发挥重要作用的可能性。事实上，这篇前沿文章描述了促食欲肽胃饥饿素激活胆碱能-多巴胺能奖赏联系，这是大脑奖赏系统中与强化相关的重要部分，从而通过该系统增加动机行为的动机显著性。我们还从临床前、临床和人类遗传学角度综述了胃饥饿素信号传导在酒精和成瘾药物诱导的奖赏中的作用。此外，本文概述了最近的研究结果，这些结果表明GLP-1可控制啮齿动物中酒精、苯丙胺、可卡因和尼古丁诱导的奖赏。最后，简要讨论了其他几种食欲调节激素在奖赏和成瘾中的作用。总体而言，这些数据表明胃饥饿素和GLP-1受体可能是开发酒精和药物依赖药物治疗的新靶点。
