Kuo D Y, Hsu C T, Cheng J T
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, ROC.
Life Sci. 2001 Dec 7;70(3):243-51. doi: 10.1016/s0024-3205(01)01401-1.
Neuropeptide Y (NPY), an orexigenic peptide, is involved in the control of food intake. Repeated administration of amphetamine (AMPH), an anorectic agent, results in an anorectic effect on day 1 and a tolerant anorectic effect on the followings. In an attempt to know the role of hypothalamic NPY in these effects of AMPH, contents of hypothalamic NPY were determined by radioimmunoassay at first. In AMPH-treated groups, the contents of hypothalamic NPY decreased rapidly on day 1 but restored gradually to the normal level on the following days as observed in repeated AMPH. An involvement of hypothalamic NPY in the feeding change of repeated AMPH can thus be considered. Moreover, daily injection of NPY antisense oligonucleotide into brain (10 microg/10 microl/day, i.c.v.) to inhibit the gene expression of hypothalamic NPY were performed at 1 hour before daily 2 mg/kg AMPH. The reversion of food intake from the anorectic level to the normal level (tolerant anorexia) was abolished by this antisense pretreatment. It is suggested that hypothalamic NPY may play a role in the change of feeding behavior induced by repeated AMPH administration.
神经肽Y（NPY）是一种促食欲肽，参与食物摄入的调控。反复给予厌食剂苯丙胺（AMPH），在第1天会产生厌食效应，而在随后几天则产生耐受性厌食效应。为了了解下丘脑NPY在AMPH这些效应中的作用，首先通过放射免疫分析法测定下丘脑NPY的含量。在AMPH处理组中，下丘脑NPY的含量在第1天迅速下降，但在随后几天逐渐恢复到正常水平，如反复给予AMPH时所观察到的那样。因此，可以认为下丘脑NPY参与了反复给予AMPH引起的摄食变化。此外，在每天给予2mg/kg AMPH前1小时，每天向脑内注射NPY反义寡核苷酸（10μg/10μl/天，脑室内注射）以抑制下丘脑NPY的基因表达。这种反义预处理消除了摄食从厌食水平恢复到正常水平（耐受性厌食）的现象。提示下丘脑NPY可能在反复给予AMPH诱导的摄食行为变化中起作用。
