ROLE OF THE GHRELIN SYSTEM IN ALCOHOLISM: ACTING ON THE GROWTH HORMONE SECRETAGOGUE RECEPTOR TO TREAT ALCOHOL-RELATED DISORDERS
ROLE OF THE GHRELIN SYSTEM IN ALCOHOLISM: ACTING ON THE GROWTH HORMONE SECRETAGOGUE RECEPTOR TO TREAT ALCOHOL-RELATED DISORDERS
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DOI：
10.1358/dnp.2010.23.3.1429490
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发表时间：
2010-04-01
影响因子：
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通讯作者：
Leggio, Lorenzo
中科院分区：
文献类型：
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作者：
Leggio, Lorenzo
存在对鉴定新的神经药理学靶点以治疗酒精依赖个体的实质性需求。Ghrelin代表肠-脑肽，最初被发现为生长激素促分泌素受体（GHS-R）的内源性配体。现有的文献清楚地表明，胃饥饿素影响食欲和食物摄入。动物和人类的研究都提供了证据，证明ghrelin不仅影响饥饿感，而且在寻找奖励物质（如酒精）方面也有作用。动物研究提供的证据表明，ghrelin刺激奖励系统，作用于特定的大脑奖励节点，并且ghrelin信号是酒精刺激奖励系统所必需的。人体研究表明，乙醇会严重影响胃饥饿素水平。有趣的是，对酒精依赖个体的人类研究表明，较高的ghrelin水平与较高的自我报告的酒精渴望测量值相关。总而言之，这些发现表明ghrelin系统在酒精依赖中起作用。胃饥饿素拮抗剂（即，GHS-R1 a拮抗剂和/或反向激动剂）可能影响酒精寻求行为，因此在酒精使用障碍中具有治疗潜力。未来的实验室和临床研究验证这一假设是必要的。
There exists a substantial need to identify new neuropharmacological targets to treat alcohol-dependent individuals. Ghrelin represents a gut-brain peptide, initially discovered as the endogenous Ligand for the growth hormone secretagogue receptor (GHS-R). The existing literature clearly demonstrates that ghrelin affects appetite and food intake. Both animal and human studies provide evidence that ghrelin not only influences hunger but also has a role in the search for rewarding substances, such as alcohol. Animal studies provide evidence that ghrelin stimulates the reward system, acting on specific brain reward nodes, and that ghrelin signaling is required for stimulation of the reward system by alcohol. Human studies show that ethanol acutely affects ghrelin levels. Interestingly, human studies with alcohol-dependent individuals suggest that higher ghrelin levels are associated with higher self-reported measurements of alcohol craving. Altogether, these findings suggest that the ghrelin system plays a role in alcohol dependence. Ghrelin antagonists (i.e., GHS-R1a antagonists and/or inverse agonists) might affect alcohol-seeking behavior, thus having therapeutic potential in alcohol use disorders. Future laboratory and clinical studies testing this hypothesis are warranted.