Badia-Elder N E, Stewart R B, Powrozek T A, Roy K F, Murphy J M, Li T K
Department of Psychology, Purdue School of Science, IUPUI, Indiana University School of Medicine, Indianapolis 46202, USA.
Alcohol Clin Exp Res. 2001 Mar;25(3):386-90.
Neuropeptide Y (NPY) deficient mice consume more ethanol than controls, whereas NPY over-expressing mice consume less ethanol than controls. Thus, ethanol drinking may be inversely associated with NPY activity. To determine whether exogenously administered NPY would alter ethanol intake, two experiments were conducted.
A within-subject design was used with intracerebroventricular (ICV) administration of NPY or artificial cerebral spinal fluid (aCSF) into the lateral ventricles. Infusions were separated by 2 to 7 days. In experiment 1, male Wistar rats (n = 10) were tested for the effects of NPY on an intake of 5% sucrose or 8% (w/v) ethanol during daily 2-hr testing periods with food and water available at all other times. In experiment 2, male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats (n = 8/line) were tested for the effects of NPY on 8% (w/v) ethanol intake.
In experiment 1, NPY (5, 10, 20 microg) significantly increased sucrose intake relative to aCSF baseline in Wistar rats, a finding consistent with previous observations of the orexigenic effects of the peptide. However, NPY (10 microg) did not alter ethanol intake in Wistar rats. In experiment 2, NPY (5 and 10 microg) significantly decreased ethanol intake in P rats, but not in NP rats.
The reduction in ethanol intake seen with the P rats is consistent with the postulated negative relationship between NPY activity and ethanol intake. The lack of effect of NPY on ethanol intake in Wistar and NP rats may be related to the lower baseline levels of ethanol intake in these rats or to differential central nervous system basal NPY activity or sensitivity to the peptide.
神经肽Y(NPY)基因缺陷型小鼠比对照小鼠摄入更多乙醇,而NPY过表达型小鼠比对照小鼠摄入更少乙醇。因此,乙醇饮用可能与NPY活性呈负相关。为了确定外源性给予NPY是否会改变乙醇摄入量,进行了两项实验。
采用受试者内设计,向侧脑室脑室内(ICV)注射NPY或人工脑脊液(aCSF)。输注间隔2至7天。在实验1中,对雄性Wistar大鼠(n = 10)进行测试,观察NPY对每日2小时测试期间5%蔗糖或8%(w/v)乙醇摄入量的影响,其他时间提供食物和水。在实验2中,对雄性嗜酒(P)和非嗜酒(NP)大鼠(n = 8/组)进行测试,观察NPY对8%(w/v)乙醇摄入量的影响。
在实验1中,相对于aCSF基线,NPY(5、10、20微克)显著增加了Wistar大鼠的蔗糖摄入量,这一发现与先前关于该肽促食欲作用的观察结果一致。然而,NPY(10微克)并未改变Wistar大鼠的乙醇摄入量。在实验2中,NPY(5和10微克)显著降低了P大鼠的乙醇摄入量,但对NP大鼠没有影响。
P大鼠乙醇摄入量的减少与NPY活性和乙醇摄入量之间假定的负相关一致。NPY对Wistar大鼠和NP大鼠乙醇摄入量缺乏影响,可能与这些大鼠较低的乙醇摄入基线水平、或中枢神经系统基础NPY活性差异、或对该肽的敏感性有关。