Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior

Neuropeptide Y (NPY) was injected directly into the paraventricular nucleus of the hypothalamus (PVN) of satiated, brain-cannulated rats, and food and water intake were measured 0.5, 1, 2, 4, and 22 hr postinjection. NPY (24, 78, 235, 783, and 2351 pmol/0.3 mul) produced a large, dose-dependent increase in food intake as well as small increase in water intake. The latency to eat was about 10 min, with substantial feeding occurring in the first 30 min. At dose below 78 pmol, the eating generally occurred only within the first hour. At doses above 235 pmol, however, the subjects' food intake continued to increase such that by 4 hr postinjection they had consumed the equivalent of normal 22-hr intake, and 22 hr postinjection they had also eaten significantly more than control subjects. Previous studies have shown that norepinephrine injected into the PVN stimulates feeding through alpha-adrenergic receptors. To investigate a possible interaction, subjects were given PVN injections of phentolamine (60 nmol) prior to injections of either NPY (78 pmol) or norepinephrine (20 nmol). Phentolamine pretreatment significantly decreased feeding elicited by norepinephrine without affecting feeding elicited by NPY. This suggests that NPY does not stimulate feeding through the release of endogenous norepinephrine. The powerful stimulation of feeding elicited by this neuropeptide suggests an important role for hypothalamic NPY, or a structurally related peptide, in the regulation of feeding behavior.