A novel neurotensin peptide analog given extracranially decreases food intake and weight in rodents

Neurotensin decreases food intake in the rat when injected into the cerebra l ventricles. We tested the effect of a novel neurotensin analog (NT69L), i njected intra-peritoneally (i.p.). on weight grain and food intake in rats. Sprague-Dawley rats (270 p) were injected i.p. with either saline or NT69L at 0.001 or 0.010 mg/kg. In further experiments, larger rats at a more ste ady state on the growth curve (400 g) were injected with either saline or 0 .010 or 1 mg/kg NT69L. Food intake, water consumption and body weight were recorded daily. Weight gain was significantly reduced in the smaller rats i njected with 0.001 or 0.010 mg/kg, showing only a 8.5 and 9.0% increase in original weight, respectively, as compared to a 29% increase fur the contro ls. The larger rats injected with 1 mg/kg, had a significant reduction in b ody weight with a 3.0% decrease in original body weight as compared to a 2. 4% increase for the controls. Food intake was significantly reduced suggest ing that the weight loss observed after injection of NT69L was attributable in part to a reduction in food intake, The genetically obese Zucker rats i njected with NT69L (1 mg/kg) had a significant reduction in weight gain and food intake. NT69L significantly increased blood glucose and corticosteron e levels and decreased TSH and Tl in Sprague-Dawley and Zucker rats, an eff ect that was only transitory. NT69L also caused a decrease in norepinephrin e in both the hypothalamus and nucleus accumbens, and an increase in dopami ne, 3,4-dihydroxyphenylacetic acid (DOPAC) and serotonin. In this study, NT 69L exhibited a consistent and dramatic effect on body weight and food inta ke in Sprague-Dawley and obese Zucker rats, and enabled us to study the rol e that NT plays in weight control and the functional interactions of NT wit h brain amines, and metabolic and endocrinological parameters. (C) 2000 Els evier Science B.V. All rights reserved.