Vickers Steven P, Dourish Colin T
RenaSci Consultancy Ltd, Pennytoot Street, Nottingham, NG1 1GF, UK.
Curr Opin Investig Drugs. 2004 Apr;5(4):377-88.
It was first established in the 1970s that the brain serotonin (5-HT) system was involved in the control of eating. Subsequent progress in the molecular pharmacology of 5-HT receptors, and the development of selective 5-HT receptor ligands, has clarified our understanding of the role of 5-HT in the regulation of ingestive behavior. Of the 14 5-HT receptor subtypes currently described, 5-HT1A, 5-HT1B and 5-HT2C receptors have been of principal interest in the regulation of food intake. This is largely due to the development of suitable agonists, antagonists and gene-knockout animals with which the role of these receptors can be elucidated. The recent development of selective ligands and knockout mice for other 5-HT receptors, including the 5-HT2B and 5-HT6 receptors, has also suggested a role for these receptor subtypes in eating behavior. Studies using such approaches should further our understanding of the role of serotonin in the regulation of feeding behavior and thus, may lead to the development of novel, safe, serotonin receptor ligands for the treatment of obesity.
20世纪70年代首次确定大脑5-羟色胺(5-HT)系统参与进食控制。随后5-HT受体分子药理学的进展以及选择性5-HT受体配体的开发,使我们对5-HT在调节摄食行为中的作用有了更清晰的认识。在目前已描述的14种5-HT受体亚型中,5-HT1A、5-HT1B和5-HT2C受体在食物摄入调节方面一直是主要研究对象。这主要归功于合适的激动剂、拮抗剂以及基因敲除动物的开发,通过它们可以阐明这些受体的作用。最近针对其他5-HT受体,包括5-HT2B和5-HT6受体的选择性配体和基因敲除小鼠的开发,也表明这些受体亚型在进食行为中发挥作用。使用此类方法的研究应能加深我们对5-羟色胺在调节进食行为中的作用的理解,因此可能会促成开发用于治疗肥胖症的新型、安全的5-羟色胺受体配体。