Intake inhibition by NPY and CCK-8: A challenge of the notion of NPY as an “Orexigen”

We tested the hypothesis that neuropeptide Y (NPY) interacts with cholecystokinin octapeptide (CCK-8) in inhibition of intake of an intraorally infused solution of sucrose, a test of consummatory ingestive behavior. Both intracerebroventricular infusion of NPY (10 μg) and intraperitoneal injection of CCK-8 (0.5 μg/kg) reduced the intake of a 1 M solution of sucrose infused intraorally at a rate of 0.5 ml/min in ovariectomized female rats, but the two peptides did not interact in inhibiting intraoral intake. By contrast, NPY increased intake if the sucrose solution was ingested from a bottle, a test demanding both appetitive and consummatory ingestive responses. CCK-8 inhibited intake in this test and its inhibitory effect was increased by simultaneous treatment with NPY. The activity in the nucleus of the solitary tract (NTS), a brainstem relay mediating inhibition of intake, judged by the expression of c-fos-like immunoreactivity, was significantly increased after treatment with CCK-8 or NPY to approximately the same extent. Combined treatment with NPY and CCK-8 did not increase the c-fos-like immunoreactivity in the NTS above treatment with NPY or CCK-8 alone. These results strengthen the hypothesis that NPY, like CCK-8, is an inhibitor of consummatory ingestive behavior and suggest that this inhibition is mediated via the NTS.