Thorsell A, Heilig M
1Department of Neuropharmacology, The Scripps Research Institute, CVN-15, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuropeptides. 2002 Apr-Jun;36(2-3):182-93. doi: 10.1054/npep.2002.0897.
Neuropeptide Y (NPY), a peptide abundantly expressed in the mammalian nervous system, has been extensively studied using traditional pharmacological and behavioral models. Central administration of NPY or synthetic ligands for its receptors has indicated a role of NPY in anxiety-related behaviors, feeding, regulation of blood pressure, circadian rhythm and other functions. Some limitations inherent in pharmacological approaches, such as lack of selectivity of receptor antagonists, can be elegantly circumvented using genetically modified animals. For NPY, mice lacking NPY, the Y1, the Y2 or the Y5 receptors have been generated. In addition, both mice and rats overexpressing NPY in the central nervous system are available. Here, we review the research carried out so far in the NPY-field using genetically modified animals. Together, these models indicate that stress-related behaviors and regulation of voluntary alcohol intake perhaps are among the most important functions of central NPY, and may provide attractive targets for developing novel therapies in depression, anxiety disorders and alcohol dependence.
神经肽Y（NPY）是一种在哺乳动物神经系统中大量表达的肽，已使用传统药理学和行为学模型对其进行了广泛研究。中枢给予NPY或其受体的合成配体已表明NPY在焦虑相关行为、进食、血压调节、昼夜节律及其他功能中发挥作用。药理学方法存在一些固有的局限性，如受体拮抗剂缺乏选择性，而使用基因改造动物可以巧妙地规避这些问题。对于NPY，已培育出缺乏NPY、Y1、Y2或Y5受体的小鼠。此外，中枢神经系统中过表达NPY的小鼠和大鼠也已获得。在此，我们综述了迄今为止在NPY领域使用基因改造动物所开展的研究。这些模型共同表明，与应激相关的行为和自愿酒精摄入的调节可能是中枢NPY最重要的功能之一，并且可能为开发治疗抑郁症、焦虑症和酒精依赖的新疗法提供有吸引力的靶点。
