Gilpin Nicholas W, Misra Kaushik, Koob George F
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, United States.
Pharmacol Biochem Behav. 2008 Sep;90(3):475-80. doi: 10.1016/j.pbb.2008.04.006. Epub 2008 Apr 16.
The anxiolytic effects of neuropeptide Y (NPY) are mediated in part by the central nucleus of the amygdala (CeA), a brain region involved in the regulation of alcohol-drinking behaviors. Centrally administered NPY suppresses alcohol drinking in subpopulations of rats vulnerable to the development of high alcohol-drinking behavior. The purpose of the current study was to determine the role of NPY in the CeA on elevated alcohol drinking produced by alcohol dependence. Adult male Wistar rats were trained to respond for 10% w/v alcohol in an operant situation with the use of a supersaccharin fading procedure. Following stabilization of responding, rats were divided into two groups matched for intake and given daily access to either alcohol-containing (9.2% v/v) liquid diet or an isocaloric control diet. Following extended access to the diet and reliable separation of operant responding between dependent and non-dependent rats during 6-h withdrawal tests, all rats were implanted bilaterally with cannulae aimed at the CeA. Rats were then infused with 4 NPY doses (0.0, 0.25, 0.5, 1.0 microg/0.5 microl aCSF) in a within-subjects Latin-square design during acute withdrawal and tested for operant alcohol responding 30 min later. Alcohol-dependent rats exhibited higher operant alcohol responding than non-dependent rats when infused with vehicle, but responding was similar in the two groups following infusion of all doses of NPY. These results indicate that NPY abolishes dependence-induced elevations in alcohol drinking and implicate the recruitment of limbic NPY systems in the motivational drive to consume alcohol following the transition to dependence.
神经肽Y（NPY）的抗焦虑作用部分是由杏仁核中央核（CeA）介导的，CeA是一个参与调节饮酒行为的脑区。中枢给予NPY可抑制易发展为高饮酒行为的大鼠亚群的饮酒量。本研究的目的是确定CeA中NPY在酒精依赖导致的饮酒量增加中的作用。成年雄性Wistar大鼠通过使用超级糖精消退程序在操作性条件下接受训练，以对10% w/v的酒精做出反应。在反应稳定后，将大鼠分为两组，根据摄入量进行匹配，并每天给予含酒精（9.2% v/v）的液体饮食或等热量的对照饮食。在延长饮食摄入时间并在6小时戒断测试期间可靠地区分依赖和非依赖大鼠的操作性反应后，所有大鼠双侧植入针对CeA的套管。然后在急性戒断期间，以受试者内拉丁方设计给大鼠注射4种NPY剂量（0.0、0.25、0.5、1.0微克/0.5微升人工脑脊液），并在30分钟后测试其对酒精的操作性反应。注射赋形剂时，酒精依赖大鼠的酒精操作性反应高于非依赖大鼠，但注射所有剂量的NPY后，两组的反应相似。这些结果表明，NPY消除了依赖引起的饮酒量增加，并表明在向依赖转变后，边缘NPY系统参与了饮酒的动机驱动。
