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孕期暴露于苯环利定的影响:母体和胎儿大脑中的分布及神经化学改变

Effects of gestational exposure to phencyclidine: distribution and neurochemical alterations in maternal and fetal brain.

作者信息

Ali S F, Ahmad G, Slikker W, Bondy S C

机构信息

Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.

出版信息

Neurotoxicology. 1989 Fall;10(3):383-92.

PMID:2576301
Abstract

Phencyclidine is a widely used drug of abuse and is known to produce a wide variety of psychoactive effects. PCP abuse by pregnant women has been reported to result in the birth of infants exhibiting irritability, jitteriness and hyperactivity with high pitched cries. The present study was designed to evaluate the distribution of PCP in the maternal and fetal brain and the neurochemical effects produced by gestational exposure. Pregnant Sprague-Dawley rats were treated sc with 5 mg/kg PCP on 3 consecutive days (GD 9-11, 12-14, 15-16, or 18-20). On gestational day (GD) 21 all rats were killed by decapitation and maternal and fetal blood was collected for PCP analysis. Brains were dissected from dams and fetuses for PCP and neurochemical analyses. On GD 21 after exposure on GD 18-20, the fetal: maternal ratio of brain PCP concentrations was 11:1. PCP exposure on GD 12-14, 15-17, and 18-20 significantly decreased fetal brain PCP binding sites on GD 21, whereas maternal values were unchanged. Fetal dopaminergic and muscarinic cholinergic receptor binding and neurotransmitter concentrations were unaffected by prenatal PCP exposure. These data demonstrated that maternal PCP exposure resulted in prolonged exposure of the developing CNS and also indicated that gestational exposure to PCP decreased high affinity binding sites of PCP in term fetal brain.

摘要

苯环己哌啶是一种广泛滥用的药物,已知会产生多种精神活性作用。据报道,孕妇滥用苯环己哌啶会导致婴儿出生时表现出易怒、紧张和多动,并伴有高音调哭声。本研究旨在评估苯环己哌啶在母体和胎儿大脑中的分布以及孕期接触所产生的神经化学效应。将怀孕的斯普拉格-道利大鼠连续3天皮下注射5mg/kg苯环己哌啶(妊娠第9 - 11天、12 - 14天、15 - 16天或18 - 20天)。在妊娠第21天,所有大鼠断头处死,收集母体和胎儿血液进行苯环己哌啶分析。从母鼠和胎儿身上取出大脑进行苯环己哌啶和神经化学分析。在妊娠第18 - 20天接触后,于妊娠第21天,胎儿大脑与母体大脑中苯环己哌啶浓度之比为11:1。在妊娠第12 - 14天、15 - 17天和18 - 20天接触苯环己哌啶,显著降低了妊娠第21天胎儿大脑中苯环己哌啶结合位点,而母体的值未改变。胎儿多巴胺能和毒蕈碱胆碱能受体结合以及神经递质浓度不受产前苯环己哌啶接触的影响。这些数据表明,母体接触苯环己哌啶导致发育中的中枢神经系统接触时间延长,也表明孕期接触苯环己哌啶会降低足月胎儿大脑中苯环己哌啶的高亲和力结合位点。

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