Freeman G, Sobotka T, Hattan D
Pharmacology and Molecular Biology Department, Battelle, Columbus, OH 43201.
Drug Chem Toxicol. 1990;13(2-3):113-33. doi: 10.3109/01480549009018116.
This study is the first in a series to define a rodent model to document the effects of amino acid-modulating compounds on central neurotransmitter function. A time-response curve for a single dose of orally intubated aspartame was determined in male Fischer 344 and Sprague-Dawley rats. Regional brain concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites were analyzed in the hypothalamus, cerebellum, pons/medulla, hippocampus, striatum, cortex, and midbrain/thalamus at 30, 60, 120, or 240 min after oral aspartame (1000 mg/kg) administration. Without consideration for time and group variables, levels of most compounds were higher in the brain regions of Fischer than Sprague-Dawley rats. Aspartame in Fischer 344 or Sprague-Dawley rats had no significant effect on levels of the catecholamines or indoleamines at any of the time points monitored following its acute administration. From the results of this study, large oral loads of aspartame do not appear to lead to regional alterations in brain biogenic amine levels.
本研究是系列研究中的第一项，旨在确定一种啮齿动物模型，以记录氨基酸调节化合物对中枢神经递质功能的影响。在雄性Fischer 344大鼠和Sprague-Dawley大鼠中测定了单剂量经口插管给予阿斯巴甜后的时间反应曲线。在口服阿斯巴甜（1000 mg/kg）后30、60、120或240分钟，分析下丘脑、小脑、脑桥/延髓、海马体、纹状体、皮质和中脑/丘脑区域脑中去甲肾上腺素（NE）、多巴胺（DA）、5-羟色胺（5-HT）及其代谢物的浓度。不考虑时间和组变量，Fischer大鼠脑区中大多数化合物的水平高于Sprague-Dawley大鼠。在急性给予阿斯巴甜后，在任何监测时间点，Fischer 344大鼠或Sprague-Dawley大鼠中的阿斯巴甜对儿茶酚胺或吲哚胺水平均无显著影响。根据本研究结果，大剂量口服阿斯巴甜似乎不会导致脑生物胺水平的区域改变。
