Butcher R E, Vorhees C V
Division of Inborn Errors of Metabolism, Children's Hospital Research Foundation, Cincinnati, OH 45229.
Neurobehav Toxicol. 1979;1 Suppl 1:207-12.
Pregnant Sprague-Dawley rats received 25 mg/kg of prochlorperazine, 20 mg/kg of fenfluramine, 75 mg/kg of propoxyphene or 200 mg/kg of diazepam daily between the 7th and 20th days of gestation. Vehicle control groups and a positive control group (vitamin A 40,000 IU/kg/day) were similarly prepared. Observations of reproductive performance were made and the offspring examined in a battery of neurobehavioral tests. Fenfluramine and prochlorperazine produced abnormalities in both the reproductive measures and neurobehavioral testing. Propoxyphene produced developmental delays and other signs of "pure" behavioral teratogenesis in that these effects were not anticipated in any of the observations of reproductive performance. Diazepam appeared to have the mildest effect on all the measurements taken. The test methods used in this study appear to be a reasonable initial approach to the development of neurobehavioral screening procedures which are comprehensive, sensitive, and usable.
在妊娠第7天至第20天期间，给怀孕的斯普拉格-道利大鼠每日分别注射25毫克/千克的氯丙嗪、20毫克/千克的芬氟拉明、75毫克/千克的丙氧芬或200毫克/千克的地西泮。同样制备了溶剂对照组和阳性对照组（维生素A 40,000国际单位/千克/天）。观察生殖性能，并对后代进行一系列神经行为测试。芬氟拉明和氯丙嗪在生殖指标和神经行为测试中均产生了异常。丙氧芬导致发育延迟和其他“纯粹”行为致畸的迹象，因为这些影响在任何生殖性能观察中均未被预期到。地西泮似乎对所有测量指标的影响最小。本研究中使用的测试方法似乎是开发全面、敏感且可用的神经行为筛查程序的合理初始方法。
