Hulsey M G, Pless C M, White B D, Martin R J
Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens 30602, USA.
Regul Pept. 1995 Oct 20;59(2):207-14. doi: 10.1016/0167-0115(95)00110-w.
Neuropeptide-Y (NPY) is a potent stimulator of feeding, and chronic administration of the peptide has been shown to increase body weight. This study determined the chronic effects of repeated daily injections of an antisense phosphorothioate oligonucleotide complementary to the rat mRNA for NPY (aNPY) on food intake, feeding behavior and body weight change in rats. Five micrograms of the aNPY oligonucleotide in ten microliters of vehicle or a missense control oligonucleotide were administered intracerebroventricularly (ICV) for seven consecutive days. Cumulative food intake, meal size and meal duration were significantly lowered in aNPY-treated animals. Body weight change of aNPY-injected animals was significantly lower than controls, and the effect was reversed after treatments ceased. A two-bottle taste aversion paradigm was employed to determine the behavioral specificity of the anorectic effect, and the phosphorothioate oligonucleotide was found not to be aversive at the dosage used. Following an additional five day injection period, animals were killed and paraventricular nuclei (PVN) were dissected. In vitro release and tissue content of NPY from this brain area were evaluated by heterologous radioimmunoassay. Content of NPY was unchanged in this brain area. Paradoxically, in vitro release of NPY was increased in aNPY-treated animals.
神经肽Y（NPY）是一种强效的进食刺激物，研究表明长期给予该肽会导致体重增加。本研究确定了每日重复注射与大鼠NPY mRNA互补的反义硫代磷酸酯寡核苷酸（aNPY）对大鼠食物摄入量、进食行为和体重变化的长期影响。将10微升溶剂中的5微克aNPY寡核苷酸或错义对照寡核苷酸连续7天脑室内（ICV）给药。aNPY处理的动物累积食物摄入量、每餐食量和进餐持续时间均显著降低。注射aNPY的动物体重变化显著低于对照组，且在停止治疗后这种效应逆转。采用双瓶味觉厌恶范式来确定厌食作用的行为特异性，发现所用剂量的硫代磷酸酯寡核苷酸并无厌恶作用。在额外的5天注射期后，处死动物并解剖室旁核（PVN）。通过异源放射免疫测定法评估该脑区NPY的体外释放和组织含量。该脑区NPY的含量未发生变化。矛盾的是，aNPY处理的动物中NPY的体外释放增加。
