Feeding response to neuropeptide Y-related compounds in rats treated with Y5 receptor antisense or sense phosphothio-oligodeoxynucleotide.

Neuropeptide Y (NPY), NPY 3-36 and pancreatic polypeptide (PP) increase short-term (2-h) food intake to varying degrees when given intracerebroventricularly (i.c.v.). Various Y receptor subtypes are proposed to participate in Y receptor ligand-induced stimulation of food intake. Here, we used an antisense phosphothio-oligodeoxynucleotide sequence (-5 relative to the initiating ATG) to the Y5 receptor subtype, which has been suggested to mediate NPY-induced feeding. Rats were treated with i.c.v. antisense or sense phosphothio-oligodeoxynucleotide for 3.5 days before NPY, NPY 3-36, or PP i.c.v. administration. The results show that antisense to the Y5 receptor had no effect on either spontaneous 2-h or NPY-, NPY 3-36-, or PP-stimulated 2-h food intake. However, there was a significant decrease relative to the sense control group in 10-h food intake following the initial 2-h feeding response to NPY (n = 10, p < 0.0001) or NPY 3-36 (n = 10, p < 0.05). The data suggest that the Y5 receptor has a modulatory role in the maintenance of feeding, but not as the critical receptor to confer for NPY and NPY 3-36 action on food intake.