NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake

Abstract

Fasting triggers a constellation of physiological and behavioral changes, including increases in peripherally produced ghrelin and centrally produced hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most species; however, hamsters primarily increase foraging and food hoarding with smaller increases in food intake. Fasting-induced increases in foraging and food hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY, and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and subsequently NPY synthesis/release, it may be that fasting-induced increased hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging, food hoarding, and food intake? This was accomplished by injecting the NPY Y1 receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or given peripheral ghrelin injections and housed in a running wheel-based food delivery foraging system coupled with simulated-burrow housing. Three foraging conditions were used: 1) no running wheel access, free food, 2) running wheel access, free food, or 3) foraging requirement (10 revolutions/pellet) for food. Fasting was a more potent stimulator of foraging and food hoarding than ghrelin. Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced increased foraging and food intake and attenuated, but did not always completely block, fasting- and ghrelin-induced increases in food hoarding. Collectively, these data suggest that the NPY Y1 receptor is important for the effects of ghrelin- and fasting-induced increases in foraging and food intake, but other NPY receptors and/or other neurochemical systems are involved in increases in food hoarding.

Fig. 1.

Values are means ± SE of foraging as a percentage of the intracerebroventricularly and intraperitoneally saline-injected controls for the effects of intraperitoneal ghrelin treatment with intracerebroventricular saline (black bars), intraperitoneal saline treatment with intracerebroventricular 1229U91 (gray bars) and intraperitoneal ghrelin treatment with intracerebroventricular 1229U91 (white bars) on hamsters without a foraging requirement and with a freely moving wheel (free wheel) (A) and with a foraging requirement (10 revolutions/pellet) (B). *P < 0.05 compared with the saline control condition.

Fig. 2.

Values are means ± SE of food intake as a percentage of the intracerebroventricularly and intraperitoneally saline-injected controls for the effects of intraperitoneal ghrelin treatment with intraventricular saline (black bars), intraperitoneal saline treatment with intracerebroventricular 1229U91 (gray bars), and intraperitoneal ghrelin treatment with intracerebroventricular 1229U91 (white bars) on hamsters without a foraging requirement and a stationary wheel (blocked wheel; A), hamsters with no foraging requirement and a freely moving wheel (free wheel; B) and hamsters with a foraging requirement (10 revolutions/pellet; C). *P < 0.05 compared with the saline control condition.

Fig. 3.

Values are means ± SE of food hoarding as a percentage of the intracerebroventricularly and intraperitoneally saline-injected controls for the effects of intraperitoneal ghrelin treatment with intraventricular saline (black bars), intraperitoneal saline treatment with intracerebroventricular 1229U91 (gray bars), and intraperitoneal ghrelin treatment with intracerebroventricular 1229U91 (white bars) on hamsters without a foraging requirement and a stationary wheel (blocked wheel; A), hamsters with no foraging requirement and a freely moving wheel (free wheel; B) and hamsters with a foraging requirement (10 revolutions/pellet; C). *P < 0.05 compared with the saline control condition.

Fig. 4.

Values are means ± SE of foraging as a percentage of the saline-injected ad libitum-fed control condition for the effects of food deprivation with intracerebroventricular saline injection (black bars) and food deprivation with intracerebroventricular 1229U91 injection (gray bars) on hamsters with a foraging requirement (10 revolutions/pellet) *P < 0.05 compared with saline-injected ad libitum control condition.

Fig. 5.

Values are means ± SE of food intake as a percentage of the saline-injected ad libitum fed control condition for the effects of food deprivation with intracerebroventricular saline injection (black bars) and food deprivation with intracerebroventricular 1229U91 injection (gray bars) on hamsters without a foraging requirement and a stationary wheel (blocked wheel; A), hamsters with no foraging requirement and a freely moving wheel (free wheel; B), and hamsters with a foraging requirement (10 revolutions/pellet; C) *P < 0.05 compared with saline injected ad libitum control condition.

Fig. 6.

Values are means ± SE food hoarding as a percentage of the saline-injected ad libitum fed control condition for the effects of food deprivation with intracerebroventricular saline injection (black bars) and food deprivation with intracerebroventricular 1229U91 injection (gray bars) on hamsters without a foraging requirement and a stationary wheel (blocked wheel; A), hamsters with no foraging requirement and a freely moving wheel (free wheel; B), and hamsters with a foraging requirement (10 revolutions/pellet; C) *P < 0.05 compared with saline injected ad libitum fed control condition.