PERINATAL POLYDRUG ABUSE--COCAINE AND ALCOHOL

最常被滥用的药物组合之一是酒精和 可卡因。这种多药摄取可能会对母亲和她造成不利影响。 子孙后代比单独消费乙醇或可卡因更多。这个 容易通过血脑屏障的强大的中枢神经系统药物也可以通过 胎盘和它们的药理作用会损害胎儿和 产前发育。 这项研究计划的主要目的是：1)检查 围产期是否同时服用酒精和可卡因 周期改变乙醇的处置、药效学和毒性 或可卡因及其代谢物在母亲和胎儿中的含量；2)评估 长期联合服用可卡因和酒精对妊娠结局的影响 在反复怀孕期间的生殖期内 第一代以及第二代和第三代动物；以及3) 确定对神经行为、生长发育的长期影响 自始至终接触可卡因和酒精对后代的影响 怀孕了。我们打算模仿母亲的真实生活情况 每天摄入一次酒精和可卡因 怀孕了。我们强烈地感觉到，这样一种“自然主义”的设计将会更加 比持续的曝光更能提供信息。 我们的假设有五个：1)乙醇和可卡因的联合给药 可能会改变可卡因在母体中的处置和药效- 因生产乙基苯甲酰ecGonine(可可烯)而导致的胎儿单位，a 酒精和可卡因联合给药的代谢产物；2) 可卡因导致血液流向某些器官的减少 可可乙烯强烈的血管收缩作用可能会加重； 3)可卡因比一种主要的可卡因--苯甲酰ecGonine更有效 代谢产物，并可能比可卡因单独在体内积累的时间更长 母亲，造成长期的不良反应。这些不利影响可能是 由于乙酯的持续形成而进一步延长 可卡因脱甲基化和脱甲基化所得的苄基淫羊藿碱 将导致该化合物积累的可卡乙烯 长时间；4)长期接触可卡因和酒精 连续怀孕可能会增加不良反应的发生率 因椰子乙烯排出缓慢而对后代造成的后遗症； 妊娠结局在第二代或第三代可能恶化。 接触毒品的母亲所生的动物。 可卡因、乙醇或两者，以及可卡因和乙烯都将被注入 静脉注射给我们建立的长期植入的清醒大鼠 模型，这将提供一个生理条件来评估 药物在人体内的药代动力学和行为学效应 母胎单位。围产期用药的远期行为效应 暴露也将被评估。 从这些研究中获得的数据将有助于更大的 了解怀孕期间滥用多种药物的风险，以及 生育期。授予=R01DA07356 合成类固醇(AS)的使用有许多有害的健康影响。 然而，青少年使用，特别是在从事高风险工作的人中 学校橄榄球(HS)的数量正在增加。因为可获得性在32 60%，1987-1991年期间使用量从1.1%增加到5.7% 在俄勒冈州的波特兰大都市区。1987年，每36个房协 橄榄球运动员声称有类固醇可用，一名学生被用作。这 每6个报告可用性增加到一个玩家使用AS 1991年。在美国，超过25万名青少年正在使用或曾经使用AS 各州。这项建议的目的是发展和评估一所学校- 以AS为基础的预防计划，旨在防止AS的启动和使用 以及其他药物对高危青少年的影响。干预的基础是 五年的前瞻性预防研究，并使用了多维， 认知-行为方法，包括AS的知识，促进AS 替代方案(营养和运动)、抵抗和沟通 技能培训。该计划干预个人、同龄人、成年人 和-环境水平。 在02、03、04和05学年，所有36岁的学生都从事足球运动 高中将按学校随机分配到两组中的一组：L A 20次干预：课堂环境中的L2，每周8次练习 培训周期或2)最低限度的信息控制。 干预组件将由教练、同行和认证人员提供 运动教练。该干预将每年重复一次，用于新的 运动员，每年为归来的运动员提供额外的助推器 在03、04和05年。教练、家长和同伴教育工作者将 接受有关计划目标和实施的指导。 调查问卷将在干预前后进行 在年终跟踪时，评估可获得性、知识、态度、 意图使用和使用AS和其他药物。态度和行为 有关营养和锻炼的内容，以及 人口统计、抵抗技能、环境因素、心理因素 构建了同伴影响和人体测量指标。计划 将通过录音带、观察来评估实施及其效果 和调查。该计划所针对的调解人之间的联系 将对药物成分和减少药物使用进行研究。两国之间的关系 具有积极和消极结果的干预组成部分(知识、 态度、意图和行为)将被确定。这项研究将 确定AS使用的保护性因素和风险因素，并提供 了解如何以及在什么条件下可以防止使用。

One of the most commonly abused drug combinations is that of alcohol and cocaine. Such polydrug ingestion may adversely affect the mother and her offspring more than the consumption of ethanol or cocaine alone. The potent CNS drugs which readily cross the blood-brain barrier also cross the placenta, and their pharmacological actions can impair fetal and prenatal development. The principal objectives of this research proposal are: 1) to examine whether co-administration of alcohol and cocaine during the perinatal period alters the disposition, pharmacodynamics and toxicity, of ethanol or cocaine and its metabolites in the mother and fetus; 2) to evaluate the pregnancy outcome with long-term Co-administration of cocaine and alcohol during the reproductive period throughout repeated pregnancies in the first as well as the second and third generation of animals; and 3) to determine the long-term effect on neurobehavior, growth and developmental outcome in the offspring after exposure to cocaine and alcohol throughout gestation. We intend to mimic the real life situation of the mother ingesting alcohol and cocaine on a once per day basis throughout gestation. We feel strongly that such a "naturalistic" design will be more informative than constant exposure. Our hypotheses are fivefold: 1) Co-administration of ethanol and cocaine may alter the disposition and pharmacodynamics of Cocaine in the maternal- fetal unit due to production of ethylbenzoylecgonine (cocaethylene), a metabolic product of the co-administration of alcohol and cocaine; 2) The decreased distribution of blood flow to certain organs produced by Cocaine may be aggravated by the strong vasoconstrictive action of cocaethylene; 3) Cocaethylene is more potent than benzoylecgonine, a major cocaine metabolite, and may accumulate longer than the cocaine alone in the mother, causing prolonged adverse effects. These adverse effects may be further prolonged by the continued ethyl ester formation from benzylecgonine derived from demethylation and deethylation of Cocaine on cocaethylene which will result in accumulation of this compound for protracted periods of time; 4) Long-term exposure of cocaine with alcohol throughout consecutive pregnancies may increase the incidence of adverse sequelae on the offspring due to slow elimination of cocaethylene; and 5) The pregnancy outcome may he worsened in the second or third generation of animals born to a drug exposed mother. Cocaine, ethanol, or both, as well as cocaethylene will be infused intravenously to our established chronically implanted conscious rat model, which will provide a physiologic condition to assess pharmacokinetic-dynamic and behavioral effects of the drugs in the maternal-fetal unit. The long-term behavioral effects of perinatal drug exposure will also be evaluated. The data obtained from these studies will contribute to a greater understanding of the risk of polydrug abuse during pregnancy and reproductive period.GRANT=R01DA07356 Anabolic steroid (AS) use has many detrimental health effects. Nevertheless, adolescent use, especially among those engaged in high school (HS) football, is increasing. AS availability has varied between 32 and 60%, with use increasing from 1.1% to 5.7% during the period 1987-1991 in the Portland, Oregon metropolitan area. During 1987, for every 36 HS football players claiming steroid availability, one student used AS. This increased to one player using AS for every 6 reporting availability in 1991. Over 250,000 adolescents are using or have used AS in the United States. The aim of this proposal is to develop and evaluate a school- based AS prevention program designed to prevent initiation and use of AS and other drugs among high risk adolescents. The intervention is based on five years of prospective prevention research and uses a multidimensional, cognitive-behavioral approach, including knowledge of AS, promoting AS alternatives (nutrition and exercise), and resistance and communication skill training. The program intervenes at the individual, peer, adult and-environmental levels. In study years 02, 03, 04 and 05, all students engaged in football at 36 high schools will be randomly assigned by school to one of two groups: l) a 20 session intervention: l2 in a classroom setting and 8 weekly exercise training periods or 2) a minimum information control. Intervention components will be delivered by coaches, peers and certified athletic trainers. The intervention will be repeated annually for new players, with additional yearly booster sessions for returning athletes during years 03, 04 and 05. Coaches, parents and peer educators will receive instruction on program objectives and implementation. Questionnaires will be administered prior to and after the intervention and at year-end follow-up, to assess availability, knowledge, attitudes, intent to use and use of AS and other drugs. Attitudes and behaviors concerning nutrition and exercise will be examined, along with demographics, resistance skills, environmental factors, intrapsychic constructs peer influences and anthropometric measures. Program implementation and its effects will be assessed by audiotape, observation and surveys. The link between mediators targeted by the program components and reduction of drug use will be studied. The relationship of intervention components with positive and negative outcomes (knowledge, attitudes, intent and behaviors) will be determined. The study will identify protective and risk factors for AS use and provide an understanding of how and under what conditions AS use can be prevented.