COCAINE: EFFECTS ON OVARIAN FUNCTION

可卡因：对卵巢功能的影响

• 批准号: 3424081
• 负责人: SUSAN J ATLAS
• 金额: $ 4.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3424081
• 关键词: autoradiography; chorionic gonadotropin; cocaine; corpus luteum; drug adverse effect; drug receptors; early embryonic stage; fertilization; intravenous administration; isolation perfusion; laboratory rabbit; oogenesis; ovary; ovulation; radioimmunoassay; reproductive system pharmacology; tritium

Society is experiencing an epidemic of cocaine use fueled by a vastly expanded supply and decreased price. Cocaine use has become more prevalent among women of child-bearing age and even pregnant women. Other than adverse effects on fetus and neonate, little is known about cocaine's effects on female reproductive function. The major objective of this proposal is to determine if exposure to intravenous cocaine impairs rabbit ovarian function. The specific aims are: (1) To determine if cocaine, administered to rabbits either as a single dose or as repeated daily injections, affects ovarian function. (2) If ovarian effects are observed, to determine if the rabbit ovary contains specific receptors for cocaine. (3) If ovarian receptors are identified, to determine the tissue receptor pattern for cocaine. Study 1 will assess if a single injection of cocaine will affect gonadotropin-induced ovulation, oocyte maturation, corpus luteum formation, fertilization and/or preimplantation embryonic development. Animals will be injected with an ovulation-inducing dose of human chronic gonadotropin (hCG) and treated with cocaine. Ovulated oocytes will be retrieved, examined for stage of maturity, and inseminated in vitro. Fertilization and preimplantation development will be monitored daily for 5 days, when normal embryos are expected to have reached the blastocyst stage. If no effect is found, Study 2 will examine if cocaine administered intravenously daily for 14 days before ovulation induction affects these parameters. Study 3 will determine if the adverse effects of cocaine on ovarian function observed in intact animals are due to direct effect on the ovary. Isolated rabbit ovaries will be perfused in vitro in the presence or absence of cocaine. Ovulation will be induced by addition of hCG to the perfusion medium and ovulated ova will be retrieved, inseminated, and monitored as in Study 1. Incubation of [3H] cocaine in the presence and absence of unlabeled drug in Study 4 will determine if observed ovarian effects are mediated through specific ovarian receptors. If high-affinity specific ovarian receptors are found, radioautography of ovarian tissue in incubated with [3H] cocaine (Study 5) will determine which ovarian tissue(s) bear receptors and therefore are potential targets for drug action. The proposed experiments will uncover adverse effects of cocaine on early reproductive events. By publicizing these adverse effects, it may be possible to convince women to abstain from cocaine before conception.

社会正在经历可卡因使用的流行病， 扩大供应，降低价格。 咖啡的使用变得越来越多 在育龄妇女甚至孕妇中普遍存在。 其他 除了对胎儿和新生儿的不良影响外，对可卡因的 影响女性生殖功能。 本项目的主要目标是 建议是确定暴露于静脉注射可卡因是否会损害兔子 卵巢功能 具体目的是：（1）确定可卡因， 以单剂量或每日重复给药于家兔 影响卵巢功能 (2)如果卵巢效应 观察，以确定兔子卵巢是否含有特异性受体， 可卡因 (3)如果卵巢受体被识别出来， 可卡因的受体模式 研究1将评估单次注射是否 可卡因会影响促性腺激素诱导的排卵，卵母细胞成熟， 黄体形成、受精和/或植入前胚胎 发展 动物将注射诱导排卵剂量的 人慢性促性腺激素（hCG）和可卡因治疗。 排卵 将取回卵母细胞，检查成熟阶段并授精 体外 将监测受精和着床前发育 每天5天，当正常胚胎预计已经达到 胚泡期 如果没有发现效果，研究2将检查可卡因是否 在诱导排卵前每天静脉给药14天 影响这些参数。 第三项研究将确定 在完整动物中观察到的可卡因对卵巢功能的影响是由于 直接影响卵巢。 将离体兔卵巢灌注在 在有或没有可卡因的情况下。 排卵将被诱导， 将hCG添加到灌注培养基中， 如研究1中那样取回、授精和监测。 [3 H]孵育 研究4中存在和不存在未标记药物的可卡因将 确定观察到的卵巢效应是否通过特定的 卵巢受体 如果发现高亲和力的特异性卵巢受体， 与[3 H]可卡因孵育的卵巢组织的放射自显影（研究5） 将决定哪些卵巢组织携带受体，因此 药物作用的潜在靶点。 拟议中的实验将揭示 可卡因对早期生殖事件的不良影响。 通过宣传 这些不利影响，也许有可能说服妇女弃权， 从可卡因中获得的