COCAINE AND REPRODUCTIVE DYSFUNCTION

可卡因与生殖功能障碍

• 批准号: 2120768
• 负责人: ROBERT S SCHENKEN
• 金额: $ 19.62万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120768
• 关键词: Macaca mulatta; cocaine; female; gonadotropins; hormone regulation /control mechanism; hypothalamic pituitary axis; menstrual cycle; ovulation; pituitary gonadal axis; sex hormones

Cocaine is a commonly abused drug among reproductive age women. there is emerging clinical evidence that chronic cocaine use in women is associated with reproductive dysfunction, including decreased libido, irregular menstrual cycles and amenorrhea. Despite the growing epidemic of cocaine abuse and evidence associating it with reproductive dysfunction, there are no control studies that have assessed the effects of chronic cocaine use on hypothalamic-pituitary-ovarian axis and menstrual cyclicity in women or subhuman primates. Studies in rats have demonstrated cocaine disrupts estrous cyclicity, decreases ovulation rates and alters hypothalamic neurotransmitters that regulate gonadotropin-releasing hormone release. Extrapolation these findings to women or subhuman primates may not be appropriate because the regulation of reproductive function differs between rodents and primates. Accordingly, this proposal will assess the effects of daily follicular phase cocaine administration on reproductive function in normally cycling rhesus monkeys. The studies proposed will: (1) characterize the dose-response effects of daily follicular-phase cocaine administration on menstrual cyclicity, gonadotropin and ovarian steroid levels, ovulation rates, and corpus luteum function, (2) characterize the effects of daily follicular-phase cocaine administration on gonadotropin pulsatility, (3) determine whether daily follicular-phase cocaine administration directly impairs pituitary gonadotropin secretion, and (4) determine whether daily follicular-phase cocaine administration directly affects ovarian steroid secretion and ovulation. To accomplish these aims, monkeys will be placed in a mobile vest and tether assembly to allow drug administration and blood sampling without anesthesia or stress which are known to impair circulating hormone levels and ovarian/menstrual cyclicity. These studies will define cocaine's disruptive effects on ovarian/menstrual cyclicity and ovulation, and determine the dose of cocaine required to disrupt cyclicity. These studies will also determine cocaine's site of action within the hypothalamic-pituitary-ovarian axis, from which future studies may better determine cocaine's mechanism of action within each site in the axis. This information will be of value in the clinical management of reproductive dysfunction related to cocaine abuse.

可卡因是育龄妇女中常见的滥用药物。 有 新出现的临床证据表明，女性长期使用可卡因与 患有生殖功能障碍，包括性欲下降、不规则 月经周期和闭经。尽管可卡因日益流行 滥用以及将其与生殖功能障碍相关的证据，有 没有对照研究评估长期使用可卡因的影响 关于女性下丘脑-垂体-卵巢轴和月经周期或 亚人类灵长类动物。对老鼠的研究表明可卡因会破坏 动情周期，降低排卵率并改变下丘脑 调节促性腺激素释放激素释放的神经递质。 将这些发现外推到女性或亚人灵长类动物身上可能并不成立 适当的，因为生殖功能的调节不同 啮齿类动物和灵长类动物之间。因此，本提案将评估 每日卵泡期可卡因给药对生殖的影响 在正常循环的恒河猴中发挥作用。拟议的研究将： (1) 表征每日卵泡期的剂量反应效应 可卡因给药对月经周期、促性腺激素和卵巢的影响 类固醇水平、排卵率和黄体功能，(2) 描述每日卵泡期可卡因给药的效果 关于促性腺激素搏动，（3）确定是否每日卵泡期 可卡因给药直接损害垂体促性腺激素的分泌， (4) 确定是否每日滤泡期可卡因给药 直接影响卵巢类固醇的分泌和排卵。为了完成 为了实现这些目标，猴子将被放置在移动背心和系绳组件中 无需麻醉或压力即可进行给药和血液采样 已知会损害循环激素水平和卵巢/月经 周期性。这些研究将确定可卡因的破坏性影响 卵巢/月经周期和排卵，并确定剂量 可卡因需要破坏周期性。这些研究还将确定 可卡因的作用部位位于下丘脑-垂体-卵巢轴内， 未来的研究可以更好地确定可卡因的作用机制 轴上每个站点内的动作。这些信息将具有价值 可卡因相关生殖功能障碍的临床治疗 虐待。