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围产期和产后暴露于2,3,7,8-四氯二苯并对二恶英:对Wistar大鼠生理发育、反射、运动活动和学习行为的影响

Peri- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on physiological development, reflexes, locomotor activity and learning behaviour in Wistar rats.

作者信息

Thiel R, Koch E, Ulbrich B, Chahoud I

机构信息

Institut für Toxikologie und Embryopharmakologie, FU Berlin, Germany.

出版信息

Arch Toxicol. 1994;69(2):79-86. doi: 10.1007/s002040050141.

Abstract

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat offspring were studied after administration of a loading dose of 300 or 1000 ng TCDD/kg body wt on day 19 of pregnancy, followed by weekly maintenance doses of 120 or 400 ng TCDD/kg body wt. The dose regimens led to a fluctuation of average TCDD concentrations in the liver of the offspring of 4.9-14.9 ng/g (TCDD1000/400 group) or 1.4-6.3 ng/g (TCDD300/120 group) during the course of the experiment. In both TCDD-exposed groups the body weight of the offspring was significantly lower on postnatal day 7 (PND 7); in the high dose group from PND 7 to PND 31. Some landmarks of postnatal development were retarded in the exposed groups; in particular, the vaginal opening was delayed for several days in both TCDD-exposed groups. The TCDD-exposed animals revealed a reduced ability to remain on a rotating rod. During reflex testing, the rate of successfully responding animals was higher in the exposed groups. No statistically significant differences in the locomotor activity between controls and TCDD-exposed offspring were detectable under our experimental conditions. In a discrimination learning test no effects on the learning ability were found. However, TCDD-exposed offspring showed an increase in unanswered trials during critical phases of the task. They also exhibited increased locomotor activity in a novel environment; prior to an amphetamine challenge dose of 1 mg/kg body weight. Amphetamine-induced activity was decreased in a dose-dependent manner.

摘要

在妊娠第19天给大鼠母体腹腔注射300或1000 ng 2,3,7,8-四氯二苯并-对-二噁英(TCDD)/kg体重的负荷剂量,随后每周给予120或400 ng TCDD/kg体重的维持剂量,研究TCDD对大鼠后代发育的影响。这些剂量方案导致实验过程中TCDD1000/400组后代肝脏中平均TCDD浓度波动在4.9 - 14.9 ng/g,TCDD300/120组为1.4 - 6.3 ng/g。在两个TCDD暴露组中,后代出生后第7天(PND 7)体重显著降低;高剂量组从PND 7到PND 31体重均降低。暴露组的一些出生后发育标志延迟;特别是,两个TCDD暴露组的阴道开口均延迟了几天。TCDD暴露的动物在旋转杆上保持平衡的能力降低。在反射测试中,暴露组成功做出反应的动物比例更高。在我们的实验条件下,未检测到对照组和TCDD暴露后代在运动活动方面有统计学显著差异。在辨别学习测试中,未发现对学习能力有影响。然而,TCDD暴露的后代在任务关键阶段未应答试验增加。在给予1 mg/kg体重苯丙胺激发剂量之前,它们在新环境中的运动活动也增加。苯丙胺诱导的活动呈剂量依赖性降低。

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