Nelson B K, Brightwell W S, MacKenzie-Taylor D R, Burg J R, Massari V J
Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, Cincinnati, OH 45226.
Neurotoxicol Teratol. 1988 Jan-Feb;10(1):15-22. doi: 10.1016/0892-0362(88)90062-1.
In addition to its widespread social use, ethanol is used extensively as an industrial solvent. Inhalation exposures to ethanol which produce narcosis in maternal rats are not teratogenic. The present study sought to extend the previous research by including offspring from paternal exposures, and testing for behavioral disorders in the offspring following maternal or paternal exposures. Groups of 18 male (approximately 450 g) and 15 female (200-300 g) Sprague-Dawley rats were exposed 7 hours/day for six weeks or throughout gestation to 16000, 10000, or 0 ppm ethanol by inhalation and then mated with untreated rats. Litters were culled to 4 males and 4 females, and were fostered within 16 hours after birth to untreated dams which had delivered their litters within 48 hours previously. Offspring from paternally or maternally exposed animals performed as well as controls on days 10-90 in tests of neuromotor coordination (ascent on a wire mesh screen, rotorod), activity levels (open field, modified-automated open field, and running wheel), and learning ability (avoidance conditioning and operant conditioning). In addition, brains of 10 21-day-old pups were analyzed for neurochemical differences from controls in concentrations of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine, substance P, Met-enkephalin, and beta-endorphin. Levels of acetylcholine, dopamine, substance P, and beta-endorphin were essentially unchanged in the offspring of rats exposed to ethanol. Complex, but significant changes in levels of norepinephrine occurred only in paternally exposed offspring. 5-Hydroxytryptamine levels were reduced in the cerebrum, and Met-enkephalin levels were increased in all brain regions of offspring from both maternally and paternally exposed rats.
除了广泛的社会用途外，乙醇还被广泛用作工业溶剂。对母鼠产生麻醉作用的乙醇吸入暴露并无致畸性。本研究试图通过纳入父方暴露的后代，并测试母方或父方暴露后后代的行为障碍，来扩展先前的研究。将18只雄性（约450克）和15只雌性（200 - 300克）的斯普拉格 - 道利大鼠分为几组，每天吸入暴露7小时，持续六周或整个妊娠期，暴露于16000、10000或0 ppm的乙醇中，然后与未处理的大鼠交配。幼崽被筛选为4只雄性和4只雌性，并在出生后16小时内寄养到之前48小时内产仔的未处理母鼠处。父方或母方暴露动物的后代在第10 - 90天的神经运动协调测试（在金属丝网屏幕上攀爬、转棒试验）、活动水平（旷场试验、改良自动旷场试验和跑轮试验）以及学习能力（回避条件反射和操作性条件反射）测试中表现与对照组相同。此外，对10只21日龄幼崽的大脑进行分析，以检测其蛋白质以及神经递质乙酰胆碱、多巴胺、去甲肾上腺素、5 - 羟色胺、P物质、甲硫氨酸脑啡肽和β - 内啡肽浓度与对照组的神经化学差异。暴露于乙醇的大鼠后代中，乙酰胆碱、多巴胺、P物质和β - 内啡肽的水平基本未变。去甲肾上腺素水平仅在父方暴露的后代中出现复杂但显著的变化。在母方和父方暴露大鼠的后代中，大脑中的5 - 羟色胺水平降低，甲硫氨酸脑啡肽水平在所有脑区均升高。
