Role of appetite-regulating peptides in the pathophysiology of addiction: implications for pharmacotherapy.
Role of appetite-regulating peptides in the pathophysiology of addiction: implications for pharmacotherapy.
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食欲调节肽在成瘾的病理生理学中的作用：对药物疗法的影响。
DOI：
10.1007/s40263-014-0178-y
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发表时间：
2014-10
期刊：
影响因子：
6
通讯作者：
Jerlhag, Elisabet
中科院分区：
文献类型：
--
作者：
Engel, Jorgen A.;Jerlhag, Elisabet
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）。Ghrelin主要从胃中释放，增加食物摄入，诱导食欲，增强肥胖以及释放生长激素。下丘脑“生长激素释放肽受体”（GHS-R1 A）在食物摄入调节中具有关键作用，但GHS-R1 A也在奖赏相关区域中表达。GLP-1在肠粘膜中以及在后脑中响应于营养摄入而产生。这种肠-脑激素减少食物摄入并调节葡萄糖稳态，主要是通过下丘脑和脑干中的GLP-1受体。然而，GLP-1受体在与奖赏调节密切相关的区域中表达。考虑到食物和药物摄入的调节具有共同的神经生物学底物，应该考虑ghrelin和GLP-1在奖赏调节中发挥重要作用的可能性。事实上，这篇领先的文章描述了食欲肽ghrelin激活胆碱能-多巴胺能奖励链接，这是大脑中与强化相关的奖励系统的重要组成部分，从而通过该系统增加了激励行为的激励显着性。我们还从临床前、临床和人类遗传学的角度综述了ghrelin信号在酒精和成瘾药物诱导的奖赏中的作用。此外，本文还综述了GLP-1对酒精、苯丙胺、可卡因和尼古丁诱导的啮齿类动物奖赏反应的调控作用。最后，简要讨论了其他几种食欲调节激素对奖赏和成瘾的作用。总的来说，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的药物治疗的新靶点。
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.
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影响因子：
9.8
作者：
Calissendorff, Jan;Danielsson, Olle;Rojdmark, Sven
通讯作者：
Rojdmark, Sven
影响因子：
16.2
作者：
Borgland, SL;Taha, SA;Bonci, A
通讯作者：
Bonci, A
DOI：
10.1073/pnas.0507480102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Boutrel, B;Kenny, PJ;de Lecea, L
通讯作者：
de Lecea, L
DOI：
10.1152/ajpendo.00582.2003
发表时间：
2004-08-01
影响因子：
5.1
作者：
Cummings, DE;Frayo, RS;Chapelot, D
通讯作者：
Chapelot, D
影响因子：
16.2
作者：
Cowley, MA;Smith, RG;Horvath, TL
通讯作者：
Horvath, TL