宫内暴露可卡因和胎鼠发育:不同给药剂量和给药时间的比较

In utero cocaine exposure and fetal development:a comparison of different dose and timing

目的 在妊娠期可卡因总给药剂量相等的情况下 ,探讨不同的给药时间及单次给药剂量对胎鼠发育的影响。方法 实验动物分为盐水对照组 (SAL)、可卡因小剂量组(COC2 0 )和可卡因中等剂量组 (COC4 0 )。妊娠 (Embryonicday ,E) 17d取材 ,记录各组胎鼠体重、脑重、纹状体重。并采用HPLC结合电化学检测器的方法测定各组胎鼠纹状体中多巴胺 (dopamine ,DA)和 5 羟色胺 (serotonin ,5 HT)的浓度。结果 COC4 0和COC2 0组胎鼠体重、脑重、纹状体重均低于SAL组 ;然而 ,仅COC4 0组胎鼠的脑 /体重比低于SAL组 (P <0 0 1)。HPLC结果表明 ,COC4 0、COC2 0组胎鼠纹状体DA、5 HT含量均高于SAL组 ,且COC4 0组纹状体 5 HT的含量显著高于COC2 0组。结论 与妊娠中晚期接触小剂量的可卡因相比 。

AIM To investigate the effects of in utero cocaine exposure on the fetal development, when fetuses were exposed to equal total dose but different dose and timing. METHODS Pregnant dams were randomly separated into three groups: SAL, COC20 and COC40. On E17, recorded body weight, brain weight and striatum weight of all groups, and examined the concentrations of DA and 5 HT in fetal striatum by HPLC. RESULTS Body weight of SAL, COC40, COC20 groups decreased progressively in turns. Brain weight of COC20 group and COC40 group was lower than that of SAL. Only the brain/body ratio of COC40 was decreased ( P <0.01). Though there was no discrepancy of the concentration of DA between COC20 and COC40 fetuses, they all had higher concentration of DA than that of SAL group. As 5 HT system in striatum was concerned, COC40 group had the highest concentration among all the groups. CONCLUSIONS We concludes that in utero cocaine exposure can induce fetal developmental delay. Compared with mid and late pregnancy low dose cocaine exposure, mid pregnancy high dose cocaine exposure leed to more severe damage of central nervous system than of other systems. We presum that the toxic effect of cocaine on the developing brain has the relationship with the alterations of DA and 5 HT system, possibly as well as other neurotransmitter system.