Ali S F, Ahmad G, Slikker W, Body S C
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Int J Dev Neurosci. 1988;6(6):547-52. doi: 10.1016/0736-5748(88)90062-7.
Pregnant Sprague-Dawley rats were treated with 5 mg/kg body weight of phencyclidine (PCP) injected at 1 ml/kg subcutaneously on three consecutive days at four different stages of gestation. Within 10-30 min after treatment, dams showed some lack of motor coordination and became lethargic. On gestational day 21, all rats were killed by decapitation and brains were dissected and stored from mother and fetus for neurochemical analysis. PCP, dopamine and muscarinic cholinergic receptor binding was measured in membranes prepared from maternal and fetal whole brain. Neurotransmitter concentrations were also measured in the fetal brain homogenates. There was a significant decrease in PCP binding sites in fetal but not maternal brains after maternal PCP injection at gestational days 12-14, 15-17 and 18-20, but not at 9-11 days. Dopamine and muscarinic cholinergic receptor binding was not significantly altered in fetal or maternal brain when compared with vehicle control animals. The whole brain dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid concentrations did not show significant change in any group studied. These data indicate that gestational exposure to PCP decreases high affinity binding of PCP in term fetal brain at doses which do not alter maternal PCP receptor binding.
将妊娠的斯普拉格-道利大鼠在妊娠的四个不同阶段连续三天皮下注射1毫升/千克体重、浓度为5毫克/千克的苯环己哌啶（PCP）。给药后10 - 30分钟内，母鼠表现出一定程度的运动协调性缺失并变得嗜睡。在妊娠第21天，所有大鼠断头处死，解剖并保存母鼠和胎儿的大脑用于神经化学分析。测定母鼠和胎儿全脑制备的膜中PCP、多巴胺和毒蕈碱胆碱能受体结合情况。还测定了胎儿脑匀浆中的神经递质浓度。在妊娠第12 - 14天、15 - 17天和18 - 20天给母鼠注射PCP后，胎儿脑而非母鼠脑中PCP结合位点显著减少，但在9 - 11天给药时未出现这种情况。与溶剂对照组动物相比，胎儿或母鼠脑中多巴胺和毒蕈碱胆碱能受体结合未发生显著改变。在所研究的任何组中，全脑多巴胺、3,4 - 二羟基苯乙酸、5 - 羟色胺和5 - 羟吲哚乙酸浓度均未显示出显著变化。这些数据表明，孕期暴露于PCP会降低足月胎儿脑中PCP的高亲和力结合，而此时母体PCP受体结合未发生改变。
