Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on feeding behaviour

Systemic injection of peptide YY3-36 reduces food intake in rodents and humans, although some groups have reported a lack of response. PYY3-36 is thought to act via the Y2 receptor to presynaptically inhibit the release of neuropeptide Y and GABA from hypothalamic arcuate neurones. Due to the controversy surrounding its action in rodents, we tested the peptide intravenously on feeding behaviour in rats and attempted to block its actions with the Y2 receptor antagonist BIIE0246. PYY3-36 significantly decreased food intake during the first hour in male Sprague-Dawley rats fasted overnight and then re-fed. BIIE0246 had no effect alone on re-feeding, but completely blocked the action of PYY3-36. In a second experiment of similar design, the behavioural satiety sequence (BSS) was studied. Normal rats eat, drink, explore and groom before entering rest. PYY3-36 significantly reduced food eaten maintaining the normal BSS, although shifting it to the left as expected for a natural satiety factor. The latency to rest occurred earlier for animals given PYY3-36 alone and PYY3-36 tended to increase the total time in rest compared with controls. These behavioural effects of PYY3-36 were blocked by BIIE0246, and BIIE0246 alone did not have an effect on the BSS. These results support the role of PYY3-36 as a natural satiety factor acting through Y2 receptors.