Ohara T, Tanaka K, Fukaya H, Demura N, Iimura A, Seno N
Sandoz Tsukuba Research Institute, Department of Pharmacology, Japan.
Behav Brain Res. 1997 Feb;83(1-2):229-33. doi: 10.1016/s0166-4328(97)86076-7.
We have clarified the effects of SDZ ENA 713 (ENA), a new phenyl-carbamate derivative, on the spatial learning impairment and neurochemical indices of central cholinergic neurons in rats. Basal forebrain (BF) lesioning with ibotenic acid markedly impaired acquisition ability in the water maze task without changing swimming rates and decreased choline acetyltransferase (ChAT) activity in the frontal cortex of rats. ENA (0.1, 0.2 mg/kg, p.o.) significantly ameliorated the impairment in acquisition ability in a dose-dependent manner. At 0.2 mg/kg, ENA prevented the reduction in ChAT activity. In normal rats, ENA (1 mg/kg, p.o.) increased extracellular ACh concentration of the prefrontal cortex. On the other hand, tissue concentrations of norepinephrine, serotonin, dopamine and their metabolites were not changed in the frontal cortex, hippocampus and striatum of normal rats. These results suggest that ENA ameliorates spatial learning disability by not only facilitating the cholinergic transmission, but normalizing impaired ChAT activity in the learning-impaired rat model.
我们已经阐明了新型苯基氨基甲酸酯衍生物SDZ ENA 713（ENA）对大鼠空间学习障碍和中枢胆碱能神经元神经化学指标的影响。用鹅膏蕈氨酸损伤大鼠基底前脑（BF）可显著损害其在水迷宫任务中的习得能力，而不改变游泳速度，并降低大鼠额叶皮质中的胆碱乙酰转移酶（ChAT）活性。ENA（0.1、0.2mg/kg，口服）以剂量依赖的方式显著改善了习得能力的损害。在0.2mg/kg时，ENA可防止ChAT活性降低。在正常大鼠中，ENA（1mg/kg，口服）可增加前额叶皮质的细胞外乙酰胆碱浓度。另一方面，正常大鼠额叶皮质、海马体和纹状体中去甲肾上腺素、5-羟色胺、多巴胺及其代谢产物的组织浓度没有变化。这些结果表明，ENA不仅通过促进胆碱能传递，而且通过使学习受损大鼠模型中受损的ChAT活性正常化来改善空间学习障碍。
