CENTRAL ADMINISTRATION OF Y5 RECEPTOR ANTISENSE DECREASES SPONTANEOUSFOOD-INTAKE AND ATTENUATES FEEDING IN RESPONSE TO EXOGENOUS NEUROPEPTIDE-Y

A number of neuropeptide Y (NPY) receptor subtypes, including the rece ntly cloned Y5 receptor, have been implicated in the stimulation of fo od intake. In the present study, Y5 receptor antisense oligodeoxynucle otides (ODNs) were used to assess the potential involvement of the Y5 receptor in the regulation of spontaneous as well as NPY-induced food intake. Repeated central administration of Y5 antisense ODN significan tly decreased spontaneous food intake and subsequently resulted in a s ignificant weight loss. Furthermore, Y5 antisense ODN pre-treatment si gnificantly inhibited the robust feeding response elicited by central administration of NPY (5.3 +/- 0.8 vs 1.08 +/- 0.28 g, vehicle +/- S.E .M. vs Y5 ODN +/- S.E.M.). The present results provide evidence that c entral Y5 receptors are involved in both spontaneous as well as NPY-in duced food intake, which may prove to be a new therapeutic route in th e treatment of obesity and other disorders of appetite.