REDUCTION OF FOOD-INTAKE IN RATS BY INTRAPERITONEAL INJECTION OF LOW-DOSES OF AMYLIN

The effect of amylin injected IP on food intake in rats of different age (7-9 weeks, 3 months, 15-18 months) was investigated. The possible site of amylin action was investigated using vagotomized rats. Lastly, the influence of food composition on amylin's effect was investigated. In 12-h food-deprived old rats, food intake was decreased significantly by amylin (1-10 mu g/kg) when injected at the beginning of the dark phase. Although the anorectic effect of amylin occurred somewhat earlier at 10 mu g/kg, no clear dose-response relationship was observed. The anorectic effect was most marked in the first 2 h after amylin injection and was compensated over 24 h. Amylin (1 and 5 mu g/kg) did not reduce food intake in undeprived old rats. In young rats, amylin (0.1-1 mu g/kg) dose-dependently reduced food intake if rats were food-deprived for 24 h, but not when deprived for 12 h. Dissection of the common hepatic vagus branch did not block the anorectic effect of amylin (age of rats: 3 months). The effect tended to last longer in vagotomized rats. The anorectic effect of amylin did not depend on the presence of carbohydrates in the diet. Water intake was not affected by amylin in water-deprived rats. In conclusion, the anorectic effect of amylin was observed at much lower doses (minimal effective dose: 0.5 mu g/kg) than reported before. These doses are similar to anorectic doses of cholecystokinin, a physiological peripheral satiety agent.