Boules M, Cusack B, Zhao L, Fauq A, McCormick D J, Richelson E
Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Brain Res. 2000 May 19;865(1):35-44. doi: 10.1016/s0006-8993(00)02187-9.
Neurotensin decreases food intake in the rat when injected into the cerebral ventricles. We tested the effect of a novel neurotensin analog (NT69L), injected intra-peritoneally (i.p.), on weight gain and food intake in rats. Sprague-Dawley rats (270 g) 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 steady 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 injected 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 for the controls. The larger rats injected with 1 mg/kg, had a significant reduction in body 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 suggesting that the weight loss observed after injection of NT69L was attributable in part to a reduction in food intake. The genetically obese Zucker rats injected with NT69L (1 mg/kg) had a significant reduction in weight gain and food intake. NT69L significantly increased blood glucose and corticosterone levels and decreased TSH and T4 in Sprague-Dawley and Zucker rats, an effect that was only transitory. NT69L also caused a decrease in norepinephrine in both the hypothalamus and nucleus accumbens, and an increase in dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and serotonin. In this study, NT69L exhibited a consistent and dramatic effect on body weight and food intake in Sprague-Dawley and obese Zucker rats, and enabled us to study the role that NT plays in weight control and the functional interactions of NT with brain amines, and metabolic and endocrinological parameters.
将神经降压素注入大鼠脑室时可减少其食物摄入量。我们测试了一种新型神经降压素类似物（NT69L）腹腔注射对大鼠体重增加和食物摄入量的影响。将体重270克的斯普拉格-道利大鼠腹腔注射生理盐水或0.001或0.010毫克/千克的NT69L。在进一步实验中，选取生长曲线处于更稳定状态的较大大鼠（400克），腹腔注射生理盐水或0.010或1毫克/千克的NT69L。每天记录食物摄入量、饮水量和体重。注射0.001或0.010毫克/千克的较小大鼠体重增加显著减少，与对照组体重增加29%相比，体重仅分别增加了8.5%和9.0%。注射1毫克/千克的较大大鼠体重显著减轻，与对照组体重增加2.4%相比，体重下降了3.0%。食物摄入量显著减少，这表明注射NT69L后观察到的体重减轻部分归因于食物摄入量的减少。注射NT69L（1毫克/千克）的遗传性肥胖 Zucker 大鼠体重增加和食物摄入量显著减少。NT69L显著提高了斯普拉格-道利大鼠和 Zucker 大鼠的血糖和皮质酮水平，并降低了促甲状腺激素和甲状腺素水平，这种作用只是暂时的。NT69L还导致下丘脑和伏隔核中的去甲肾上腺素减少，多巴胺、3,4-二羟基苯乙酸（DOPAC）和血清素增加。在本研究中，NT69L对斯普拉格-道利大鼠和肥胖 Zucker 大鼠的体重和食物摄入量表现出一致且显著的影响，并使我们能够研究神经降压素在体重控制中的作用以及神经降压素与脑胺、代谢和内分泌参数之间的功能相互作用。
