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.