Exposure In Utero Cocaine Exposure On The Offspring Dopaminergic Nervous System Development And Function Of The Impact

OBJECTIVEThere are 1 ~2% newborns exposed cocaine in uterus every year in world. In fact, the ratio of cocaine abuse during pregnancy is much high than this. Lots of clinical materials indicated that pregnant cocaine exposure raise premature rate, abortion rate and birth death rate strongly. The weight, body and head circumference of the infants exposed cocaine are much lower than normal. They show different behavior abnormal to some extent. Those "cocaine infants" put heavy load on families and society. Thus, it' s not only one of medical problem but also a kind of social question to research the neural toxicity effect of pregnant cocaine exposure on offspring.In general, DAS is regarded as one of main action target of cocaine . The research relate to pregnant cocaine exposure are much limited to fetus level animal model. Some researches find that pregnant cocaine exposure result in abnormal development of fetus' brain, such as the disorder of neuron structure and stratification. Many other experiments find that cocaine can lesion monoaminic neurotransmitter. Are these changes temporary or continuing? The animal model about it is poor. Epidemiological data indicated that the school age children who exposed to cocaine before birth manifest such abnormal nervous behaviors as poor acceptance , inattention , and decent of understanding. From above, we can cue that cocaine has long toxicity effect on CNS.The main aim of this experiment is to study the long effect of pregnant cocaine exposure on offspring from the aspect of neurobio-chemistry, neuropsychology and monology by building a mice animal model exposed to cocaine pregnantly. We also research the dose -and age - dependence of cocaine toxicity. In addition, we study the plasticit character of nervous phylogenesis by give another injection of cocaine to the offspring. It is important for us to clarificate the neuro-toxic effect mechanisms of pregnant cocaine exposure so that we can improve the prevention and treatment of cocaine addition cases and relieve the load of families and society.METHODESAdult mice mated by rate of 4:1 ( : ) at the room temperature of ( 24 1) . Female mice were given examination of vagina at 7 ;00 and 19 ;00 the followingday. Those whose pessus positive or vaginal smear positive were pregnant and labeled ?. The pregnant mice were divided to COC10, COC20, COC40,SAL groups at random. Every pregnant mice gave 10 mg kg-1 d-1(COC10),20 mg kg-1 d-1(COC20) ,40 mg - kg-1 d-1(COC40) or same volum saline (SAL)twice a day at 7:30 and 19:30 during E8 -E17. the first day of parturition of pregnant mice was labeled P0. All offspring deliver to normal mother feeding. All offspring were ablactated and separated by sex on P22. We detected DA, DOPAC and HVA in offspring' brains by means of HPLC on P10, P35 and P65; observed the distribution and relative content of TH of SN and VTA areas in the way of immuno-histochemistry technology; investigated the structure of frontal lobe contex by toluidine blue staining; studied the ability of space distinguish of offspring by using of water maze; detected the effect of another cocaine injection on DA and it's metabolites by HPLC.RESULTSThe main part of pregnant mice in the COC40 groups were abortion. Their survival were all dead before P10. The weight of body and brain of offspring from COC20 were lower than from SAL. The content of DA, DOPAC and HVA of offspring' brains from COC20 were higher than from SAL groups on-P10, P35.. In addition, their TH immu-noreaction in SN and VTA areas were stronger then. The brain section from COC20 displayed disorder neuron level and delection of nucleo-lus. Their pyramidal cell manifest obvious dysplasia. What' s more , the latency of finding platform from COC20 was longer than from SAL groups on P35. The changes in COC20 above recovered on P65. There was no statistical difference from COC10. The coctent of DA and its metabolites were all elevated after another cocaine injection. While there existed a low raising - percentage.CONCLUTI...