FETAL COCAINE EXPOSURE; EFFECT ON NEONATAL BREATHING

该提案将首先确定下列物质的半衰期、清除率和体积： 可卡因在妊娠豚鼠体内的分布 在妊娠的最后三分之一注射。 这些药代动力学数据 将用于确定皮下注射可卡因的输注速率 通过渗透泵给药。 可卡因在大坝中的清除将是 在皮下输注研究期间验证。 科克伦及其两个 代谢物，苯甲酰芽子碱和去甲可卡因，将通过反相色谱法测定。 离子对高效液相色谱法（HPLC） 紫外检测 计算机化气相色谱/质谱 将用于检查标准品的纯度并补充HPLC 用于鉴定其他代谢物的分析。 的最终目的 建议是确定胎儿可卡因暴露对胎儿的影响。 新生豚鼠呼吸的神经控制。 三剂 可卡因和安慰剂治疗将由 四组动物的静脉途径，并以恒定的速度， 在另外四个中，用渗透泵皮下给药途径 组 治疗分配将是随机分配。 呼吸 将通过无创体积描记法在清醒状态下进行评估。 新生动物暴露于可卡因或安慰剂治疗， 子宫。 将分析新生儿呼吸模式，同时动物 呼吸室内空气 呼吸的化学控制将通过以下方式进行评估： 研究高碳酸血症的呼吸反应。 行为调节 呼吸将被评估为皮层电活动的函数， 睡眠状态 将分析新生儿呼吸的生理变化 关于可卡因剂量-反应特性以及 可卡因给药途径。 呼吸研究很重要 为育龄妇女提供教育和咨询， 滥用药物的母亲和她们的婴儿。 这些研究尤其 重要的是，滥用药物母亲的婴儿，包括 仅使用可卡因的人，有异常的睡眠模式， 婴儿猝死综合症（SIDS）的风险增加。

The proposal will first determine the half-life, clearance and volume of distribution of cocaine in the pregnant guinea pig following intravenous injection during the last third of gestation. This pharmacokinetic data will be used to determine infusion rates for subcutaneous cocaine administration by osmotic pump. Clearance of cocaine in the dam will be verified during a subcutaneous infusion study. Cocaine and two of its metabolites, benzoylecgonine and norcocaine, will be determined by reverse phase, ion-pair high performance liquid chromatography (HPLC) with ultraviolet detection. Computerized gas chromatography/mass spectrometry will be used to check purity of standards and to supplement the HPLC analysis for identification of other metabolites. The ultimate aim of the proposal is to determine the effect of fetal cocaine exposure upon the neurological control of breathing in neonatal guinea pigs. Three doses of cocaine and a placebo treatment will be given intermittently by the intravenous route in four groups of animals and at a constant rate by the subcutaneous route of administration with an osmotic pump in another four groups. Assignment of treatments will be random allocation. Breathing will be assessed by a noninvasive plethysmographic method in conscious neonatal animals who have been exposed to cocaine or placebo treatment in utero. Neonatal ventilatory patterns will be analyzed while the animal breathes room air. Chemical control of breathing will be assessed by studying the breathing response of hypercapnea. Behavioral modulation of breathing will be evaluated as a function of electrocortical activity and sleep state. Physiological changes in neonatal breathing will be analyzed with respect to cocaine dose-response characteristics as well as to the route of cocaine administration. The breathing studies will be important for educating and counseling women of child bearing age and in caring for substance-abusing mothers and their infants. These studies are especially important since infants of substance-abusing mothers (ISAM) including cocaine-only users, have abnormal sleeping ventilatory patterns and may have an increased risk of sudden infant death syndrome (SIDS).