| PrefaceAbout 10 -20% newborn has exposed to cocaine in utero in the world. In fact, the number of mothers who use cocaine during pregnancy is much more. So to investigate the effects of cocaine on fetal development is not only a medical problem, but also a social one.Newborn exposed to cocaine in utero has different neurobehavior-al impairments, from weak temporary behavior disorders to severe retardation of growth and intelligence.However, under the condition that the total dose is equivalent, it is inconclusive that whether different - dose and different - period cocaine exposure has various effects on fetal development. In our study, we compared the effects of mid - pregnancy medium - dose cocaine exposure with the effects of mid - and late - pregnancy low - dose cocaine exposure on fetal development to clarify whether different - dose and different - period cocaine exposure has different effects. Our research will provide academic basis to guide abusive mother to cut down cocaine dosage during pregnancy and to reduce the birth rate of "cocaine babies". In recent years, more and more researchers have noticed that to clear the mechanism in which cocaine exposure in utero leads to neurobehavioral impairments of offspring is very important. A-mong many candidate mechanisms, the alterations of monoaminergic system received more attention. So we used HPLC analysis method to detect the concentrations of DA and 5 - HT to help clarify the mecha-nism in which cocaine acts on developing brain. Meanwhile, we set up pair - fed groups to elucidate the effects of maternal undernutrition in the process of pregnancy cocaine exposure on the development.MethodsPregnant dams were separated into five groups; one to receive cocaine at 10 mg/kg twice daily from E8 - 17 with food ad lib( C I ) ; one to receive cocaine at 20 mg/kg twice daily from E8 - 12, and then receive saline at 10 ml/kg twice daily from E13 -17 with food ad lib ( C II ) ; one to receive saline at 10 ml/kg twice daily and be pair - fed with C I dams from E8-17 (SI ); one to receive saline at 10 ml/kg twice daily and be pair - fed with C II dams from E8-17 (S II) and one to receive saline at 10 ml/kg twice daily from E8 - 17 with food ad lib ( SAL). Recorded maternal food intake, weight gain, gesta-tional length, litter size and the ratio of dead and displastic fetuses, as well as fetal body weight, brain weight and striatum weight. Meanwhile , we analyzed concentrations of cocaine in plasma and DA and 5 - HT in striatum by HPLC. Besides, morphologic alterations of fetal brain, liver and placenta by HE and toluidine blue staining were observed.ResultsCompared with variables of SAL group, maternal weight gain of C I , C II , S I , S II groups increased slowly, while reductions of fetal body weight, brain weight and striatum weight were only seen in C I and C II groups ( P <0.01). The rate of maternal abortion and the ra-tio of dead and displastic fetuses of C H group increased remarkably, in comparison with C I group. Though body weight and brain weight of C I pups was a bit lower than C II group, the ratio of striatum weight/ brain weight of C II pups was the lowest. HPLC analysis showed concentrations of DA, 5 - HT in the striatum of C I and C E groups were much higher than those in the other groups ( P < 0. 01) , as well as augmentation of 5 - HT of C H pups was much more than that of C I pups. After observed morphologic alterations, we found cells in the striatum and cingulate cortex II of C I and C II groups distributed mus-sily and boundaries between cells in these two groups were vague. But morphologic alterations of cingulate cortex I were only seen in C II group. In liver, less number of hepatocytes, disorganized hepatocellu-lar cords and blurry structure of hepatic lobes could be seen in the C I and C II groups. Meanwhile, we observed morphologic alterations of placenta in the C I group; that is, less number of villi, hypogenesis of villi and narrow caliber of vessels.DiscussionIt is unclear that whether different -... |