THIRD TRIMESTER MODEL OF PRENATAL COCAINE EXPOSURE

近年来，可卡因滥用的发生率急剧增加， 年 可能有一个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，产前可卡因暴露可能会产生不良影响。 对发育中的后代的影响。 这项建议的目的是 开发一个啮齿动物模型，观察可卡因暴露的影响， 相当于人类的妊娠晚期 这是一个快速发展的时期 中枢神经系统（CNS）生长和增殖通常被称为 称为"大脑快速增长"。 有数据表明，这一时期 可能对可卡因诱导的中枢神经系统作用特别敏感。 在 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， 在人类怀孕的第三个三个月，可卡因必须 给新生大鼠注射。 给药可卡因， 将采用人工饲养程序， 植入胃内插管，并喂食配方奶， 将采用人工饲养程序植入幼崽 通过该方法，将胃内插管植入幼鼠体内， 配方中加入药物。 这样做的一个主要优点是 人工饲养的方法是，每天消耗的食物量是 由实验者控制，从而完全控制可卡因 没有任何伴随营养不良的风险。 后 确定适当剂量（将选择低剂量和高剂量 在确定适当剂量后（低剂量和高剂量将 在剂量反应研究后选择），将 考察 因为有初步数据表明可卡因暴露 婴儿表现出运动和平衡缺陷，一些任务，评估 将检查运动发展、协调和平衡。 此外，本发明还提供了一种方法， 评估哺乳行为和联想学习。 最后， 由于儿茶酚胺能系统经历大量的生长 和增殖在这个"大脑生长冲刺"，药理学 评估儿茶酚胺能神经递质的功能完整性的挑战 系统将进行检查。 这些发现可以提供重要的 关于中枢神经系统对可卡因的敏感性的信息， 妊娠晚期 如果这个发育期对 可卡因损伤（如预测），这些发现将提供进一步的 药物治疗和教育的重要性的证据 怀孕

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.