可卡因对后代多巴胺能神经系统的长时影响:剂量依赖性与年龄依赖性研究  

Long-term effects of pregnant cocaine exposure on the offspring dopaminergic nervous system development: research of dependence on dose and age

作　　者：关晓伟[1] 宋君[1] 翟秀岩[2] 任嘉谦[3] 何威[1] 

机构地区：[1]中国医科大学组织学与胚胎学教研室,沈阳110001 [2]中国医科大学发育生物学研究室,沈阳110001 [3]中国医科大学脑研究所,沈阳110001

出　　处：《中国药理学通报》2003年第4期392-396,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题 No 39970 772

摘　　要：目的　通过建立妊娠中晚期暴露于可卡因的小鼠动物模型 ,探讨可卡因对后代多巴胺能神经系统 (dopaminergicnervoussystem ,DAS)的发育是否具有长时程影响 ,同时探讨这种影响是否具有剂量依赖性和年龄依赖性。方法　称量不同剂量可卡因处理组与对照组的后代仔鼠在青春前期、青春期和成年期的体重和脑重 ;运用高效液相色谱结合电化学检测器 (HPLC EC)的技术检测各组各时期后代仔鼠脑内多巴胺 (dopamime,DA)及其代谢产物 3 ,4 双羟苯乙酸 (3 ,4 di hydroxyphenylaceticacid ,DOPAC)、高香草酸 (4 hydroxy 3 menthoxyphenylaceticacid ,HVA)含量差异 ;通过免疫组织化学结合图像分析方法观察黑质区 (substantianigra,SN)酪胺酸羟化酶 (tyrosinehydroxylase,TH)的分布与含量。 结果　在妊娠期中晚期皮下注射中等剂量可卡因的仔鼠在青春前期和青春期生长发育延迟 ,脑内DA及其代谢产物的含量比对照组明显增高 ,SN区TH相对含量增多 ,这些改变在成年期恢复正常 ;低剂量组的仔鼠各项检测指标在各时期与对照组相比无统计学意义 ;高剂量组的妊娠母鼠流产率为 80 % ,新生仔鼠 1 0d内死亡。结论　妊娠期暴露于可卡因对后代DAS的发育和功能具有长时程影响 。AIM To develop a murine model for investigating the long term effects of pregnatal cocaine exposure on the offspring dopaminergic nervous system and their relationships with dose and age. METHODS The body and brain weight of offspring from COC10, COC20 and SAL groups was measured. The concentration of dopamine and its metabolites were analyzed by HPLC EC. The distribution and relative content of TH in SN region was observed by immunochemistry. RESULTS During preadolescence and adolenscence, cocaine induced development delay of offspring from COC20;neurotransmitter analysis revealed that the concentration of DA,DOPAC,HVA in the brains from COC20 prepups and pups is much higher than that from controls. There were no significant differents between COC10 and SAL groups. The rate of abortion from COC40 was 80%,the other neonates all died before P10. CONCLUTION Pregnatal cocaine exposure can lead to long term effects on offspring dopaminergic nervous system. These effects are dose and age dependent.

关 键 词：可卡因 妊娠 多巴胺 酪胺酸羟化酶 

分 类 号：R－332[医药卫生] R322.8