Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.

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Mild tail pinch (TP) in rats resulted in 72% of animals displaying ingestive behavior with 20% demonstrating gnawing behavior without food ingestion and 8% demonstrating licking behavior only. The animals ate steadily over 5 min with a maximum rate occurring at 1 min (0.5 +/- 0.2 g). There was a circadian rhythm of TP-induced behavior with the peak food ingestion occurring at 24 h. A mild increase in blood glucose occurred 120 s after commencement of TP (115 +/- 4 mg/dl). Common satiety signals such as stomach distension and glucose decreased food ingestion. Parenteral administration of glucagon, cholecystokinin-octapeptide, bombesin, and thyrotropin-releasing hormone resulted in suppression of TP-induced food ingestion. Chronic TP (12 5-min TP periods/day) resulted in a fall in spontaneous food intake with the total intake remaining similar to food intake prior to the chronic TP period. We suggest that TP serves as an excellent model for eating behavior because 1) it correlates well with starvation-induced eating; 2) it precludes the necessary deprivation of food and water to adrenalectomized animals; and 3) animals subjected to TP continue chewing in the face of decreased food intake allowing one to exclude the possibility that the effects of an anorectic are secondary to nausea.

Our aims were to further characterize the stimulatory effect of glucagon on brown fat and to test the hypothesis that physiological levels of hyperglucagonemia would stimulate brown fat thermogenesis. In the first set of experiments, glucagon (1 mg/kg sc twice daily) or vehicle control was administered three times in 26 h. This large dose of glucagon produced increases in GDP binding to brown fat mitochondria. In addition, Scatchard analysis indicated a glucagon-induced increase in number of GDP binding sites without evidence for alteration in binding site affinity. No consistent increase in brown fat mitochondrial GDP binding was produced 2 h after a single injection of glucagon (1 mg/kg). In the second set of experiments, glucagon was administered intraperitoneally by constant osmotic minipump infusion. Glucagon in a dose of 150 micrograms.kg-1.day-1 for 5 days produced significant increases in GDP binding to brown fat mitochondria, whereas glucagon serum levels were increased but stayed within the usual physiological range. A larger dose of glucagon administered by constant infusion virtually eliminated body weight gain over 7 days while significantly increasing nucleotide binding (GDP) to brown fat mitochondria. An important role for glucagon in thermogenic regulation is suggested.

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