Coulombe R A, Sharma R P
Toxicol Appl Pharmacol. 1986 Mar 30;83(1):79-85. doi: 10.1016/0041-008x(86)90324-8.
The dipeptide aspartame (NutraSweet) is a newly approved and widely used artificial sweetener in foods and beverages. Consumption of aspartame (ASM) has been reported to be responsible for neurologic and behavioral disturbances in sensitive individuals. Unfasted male CD-1 mice were dosed orally with 13, 130, or 650 mg/kg ASM in corn oil, while control animals received corn oil alone. Three hours after dosing, the animals were killed, and the concentrations of the catecholamines norepinephrine (NE) and dopamine (DA), catecholamine metabolites 3-methoxy-4-hydroxymandelic acid (VMA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), the indoleamine serotonin (5-HT), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined by electrochemical high-performance liquid chromatography in six brain regions. ASM exerted its primary effect on adrenergic neurotransmitters in various brain regions. In the hypothalamus, the region richest in NE, increases in NE concentrations of 12, 49, and 47% were found in the low, medium, and high dose groups, respectively, relative to control. Significant increases of NE in the medulla oblongata and corpus striatum were also observed. Increases of the catecholamine DA and catecholamine metabolites VMA, HVA, and DOPAC were seen in various regions. The indoleamine serotonin and its metabolite 5-HIAA were unaffected by ASM treatment. These findings are consistent with ASM-induced increases in the brain catecholamine precursor amino acids phenylalanine and tyrosine, as reported earlier. Such observed alterations in brain neurotransmitter concentrations may be responsible for the reported clinical and behavioral effects associated with ASM ingestion.
二肽天冬甜素（纽甜）是一种新获批并广泛用于食品和饮料中的人工甜味剂。据报道，敏感个体食用天冬甜素（ASM）会导致神经和行为紊乱。未禁食的雄性CD-1小鼠经口给予13、130或650mg/kg ASM的玉米油溶液，而对照动物仅给予玉米油。给药3小时后，处死动物，通过电化学高效液相色谱法测定六个脑区中儿茶酚胺去甲肾上腺素（NE）和多巴胺（DA）、儿茶酚胺代谢物3-甲氧基-4-羟基扁桃酸（VMA）、高香草酸（HVA）和二羟基苯乙酸（DOPAC）、吲哚胺5-羟色胺（5-HT）及其代谢物5-羟基吲哚乙酸（5-HIAA）的浓度。ASM对不同脑区的肾上腺素能神经递质产生主要影响。在下丘脑这个NE含量最丰富的区域，低、中、高剂量组的NE浓度相对于对照组分别增加了12%、49%和47%。在延髓和纹状体中也观察到NE显著增加。在各个区域都观察到儿茶酚胺DA以及儿茶酚胺代谢物VMA、HVA和DOPAC增加。吲哚胺5-羟色胺及其代谢物5-HIAA不受ASM处理的影响。这些发现与之前报道的ASM导致脑儿茶酚胺前体氨基酸苯丙氨酸和酪氨酸增加一致。如此观察到的脑内神经递质浓度变化可能是与摄入ASM相关的临床和行为效应的原因。
