THIRD TRIMESTER MODEL OF PRENATAL COCAINE EXPOSURE

可卡因滥用的发生率在最近几年急剧增加 好几年了。可能有一项更可怕的统计数据表明 可卡因可能是孕妇最常滥用的药物之一 这表明接触可卡因的婴儿数量可能正在增加。 现有的数据表明，产前接触可卡因可能会对 对发育中的后代的影响。这项建议的目的是 建立一种啮齿动物模型来观察可卡因暴露的影响 相当于人类的晚期妊娠。这是一段快速发展的时期 中枢神经系统(CNS)的生长和增殖通常指 被称为“大脑发育急速增长”。有数据表明，这段时间 可能对可卡因对中枢神经系统的影响特别敏感。在……里面 大鼠，类似的发育期发生在前两周 出生后。因此，为了研究可卡因暴露的影响 在人类怀孕的最后三个月，可卡因必须 给新生大鼠注射。为了给新生儿服用可卡因，一个 幼崽将采用人工饲养程序 植入了胃插管，并喂食了一种奶粉 幼崽被植入一种人工饲养程序将被采用 通过这种方式，幼崽被植入胃内插管并喂食牛奶 配方中添加了药物的配方。这样做的一个主要优势是 人工饲养的方法是每天消耗的食物量是 由实验者控制，从而允许完全控制可卡因 暴露于无任何伴随的营养不良风险。紧随其后的是 确定适当的剂量(将选择低剂量和高剂量 在确定适当的剂量之后(低剂量和高剂量将 在剂量-反应研究之后选择)，一些行为将被 检查过了。因为有初步数据表明，接触可卡因 婴儿表现出运动和平衡障碍，这是一系列评估任务 将考察运动的发展、协调和平衡。此外, 吸奶行为和联想学习将被评估。最后， 因为儿茶酚胺能系统经历了大量的生长 以及在这种“脑生长激增”期间的增殖，药理学 评估儿茶酚胺能功能完整性的挑战 将对系统进行检查。这些发现可能会提供重要的 有关中枢神经系统对可卡因敏感性的信息 怀孕第三个月。如果这一发育期对 可卡因伤害(正如预测的那样)，这些发现将提供进一步的 药物治疗和教育重要性的证据 怀孕了。

The incidence of cocaine abuse has increased dramatically within recent years. Probably one of the more frightening statistics suggest that cocaine may be one of the most frequently abused drugs by pregnant women suggesting that the number of cocaine-exposed infants may be increasing. The available data suggest that prenatal cocaine exposure may have adverse effects on the developing offspring. The purpose of this proposal is to develop a rodent model to look at the effects of cocaine exposure during the equivalent of the human third trimester. This is a period of rapid central nervous system (CNS) growth and proliferation commonly referred to as the "brain growth spurt". There are data that suggest that this period may be particularly sensitive to cocaine-induced effects on the CNS. In rats, the analogous developmental period occurs during the first two weeks after birth. Therefore, in order to study the effects of cocaine exposure during the third trimester of human pregnancy, cocaine must be administered to the neonatal rat. To administer cocaine neonatally, an artificial-rearing procedure will be employed by which the pups are implanted with an intragastric cannula and fed a milk formula which the pups are implanted with an artificial-rearing procedures will be employed by which the pups are implanted with an intragastric cannula and fed a milk formula with the drug added to the formula. A major advantage of this artificial-rearing method is that the amount of food consumed daily is controlled by the experimenter thus allowing complete control over cocaine exposure without any risk of concomitant undernutrition. Following the establishment of appropriate doses (a low and a high dose will be chosen following the establishment of appropriate doses (a low and high dose will be chosen following a dose-response study), a number of behaviors will be examined. Since there are preliminary data suggesting that cocaine-exposed infants exhibit motor and balance deficits, a number of tasks that assess motor development, coordination and balance will be examined. In addition, suckling behavior and associative learning will be assessed. Finally, since the catecholaminergic system undergoes a substantial amount of growth and proliferation during this "brain growth spurt", pharmacological challenges which assess the functional integrity of the catecholaminergic system will be examined. These findings could provide important information regarding the sensitivity of the CNS to cocaine during the third trimester. If this developmental period is particularly sensitive to cocaine injury (as is predicted), these findings would provide further evidence of the importance of drug treatment and education during pregnancy.