Received 2001-12-13 Accepted 2002-04-12

This project was supported by the National Natural Science Foundation of China (No. 39970772).

*Corresponding author. Tel: +86-24-23261454; Fax: +86-24-23254417; E-mail: hwei100@yahoo.com.cn

Acta Physiologica Sinica Aug. 2002, 54 (4), 342~348

Research Paper

Effects of pregnancy cocaine exposure on the mother and fetus: a murine model

SONG Jun1, GUAN Xiao-Wei1, REN Jia-Qian2, HE Wei1,*

1Department of Histoembryology, China Medical University, Shenyang 110001, China; 2Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA

Abstract: The aim of the experiments was to develop and characterize a murine model for investigating the effects of prenatal cocaine exposure on the mother and fetus. Pregnant mice were separated into three groups: group 1 was treated with cocaine HCl at 10 mg/kg twice daily (COC); group 2 was treated with saline at 10 ml/kg twice daily (SAL); and group 3 was pair-fed with the COC dams and was injected with saline following the same schedule (SPF) from embryonic day (E) 8 to 17. We utilized high-pressure liquid chromatography (HPLC) with UV detector and electrochemical detector to test the concentrations of cocaine, dopamine and serotonin, as well as HE staining to observe morphological alterations of liver and placenta. Though less food intake and lower weight gain were observed in COC and SPF groups but not in SAL dams, lower fetal body weight and brain weight were only seen in COC offspring. Pharmacological analysis revealed that cocaine was found in fetal plasma at 15 min following intraperitoneal administration on E17, accompanied with elevated concentrations of dopamine (DA) and serotonin (5-HT) in fetal brain. We also observed morphological changes in liver and placenta of cocaine-exposed fetuses. The present study indicates that pregnancy cocaine exposure can lead to maternal undernutrition and developmental abnormality of the fetal brain, liver and placenta. It is suggested that the developmental abnormality of the fetuses induced by cocaine is due to the toxicological effect of cocaine but not to maternal undernutrition.

Key words: cocaine; pregnancy; maternal exposure; fetus; neurotransmitters; fetal development; chromatography; high pressure liquid

妊娠期给予可卡因对母体和胎儿的影响: 小鼠动物模型

宋 君1, 关晓伟1, 任嘉谦2, 何 威1,*

1中国医科大学组织胚胎学教研室, 沈阳 110001; 2哈佛大学麻省总医院神经科研究室, 美国

摘 要: 探讨妊娠期给予可卡因对母体和胎儿的影响。妊娠小鼠分为3组：可卡因注射组(每日两次注射盐酸可卡因10 mg/kg, COC); 盐水对照组(每日两次注射生理盐水10 ml/kg, SAL); 饮食对照组(每日两次注射生理盐水10 ml/kg, 饮食参考可卡因给药组, SPF)。用高压液相色谱分析法检测胎鼠血中可卡因浓度及纹状体中神经递质多巴胺和5-羟色胺的含量, 并结合HE染色观察胎鼠肝脏和胎盘的形态学改变。尽管COC和SPF组母鼠摄食量和体重增长量均降低, 但是仅仅COC组胎鼠的体重和脑重减少。高压液相色谱分析结果显示, 在COC组胎鼠血浆中可检测出可卡因, 并伴有纹状体神经递质含量的异常增高。同时, 也观察到了COC组胎盘和肝脏的形态学变化。本研究表明, 妊娠期给予可卡因能引起妊娠母体营养不良, 子代脑、肝脏和胎盘发育异常; 可卡因引起的胎儿发育异常是由可卡因的毒性作用而不是母体营养不良产生的。

关键词: 可卡因; 妊娠期; 母体给予; 胎儿; 神经递质; 胎儿发育; 高压液相色谱

学科分类号: Q954.6; R332; R992