POLYDRUG ABUSE IN WOMEN: NIDA CLINICAL RESEARCH CENTER

青年男女滥用可卡因是一个主要的公共卫生问题。 今天。许多医学疾病都与可卡因有关 虐待和依赖，包括生殖功能障碍 (高催乳素血症、闭经、黄体功能不全、男性阳萎)； 妊娠异常和围产期发育受损；生命 威胁脑血管和心血管的异常以及 免疫功能受损，增加感染疾病的风险 包括艾滋病。建议继续我们的NIDA临床研究 中心，“女性中的多药滥用”关注神经内分泌 可卡因滥用的后果以及新的临床前评估 治疗可卡因滥用和多药滥用的药物。可能的 可卡因不良生物易感性的性别差异 结果将通过纳入男性和女性进行评估 研究对象。科学和国会的担忧最近汇聚到了 强调研究女性和男性的重要性。 我们建议对慢性前列腺癌的影响进行参数评估。 可卡因滥用和对神经内分泌激素的依赖 女性和灵长类动物的平行研究中的正常生殖功能 模特。高催乳素血症通常与可卡因滥用有关，并可能 影响免疫功能。可卡因刺激促肾上腺皮质激素(ACTH) 随后可能改变免疫功能和敏感性的分泌物 用于包括艾滋病在内的传染病。基于计算机的脉冲频率 血清促肾上腺皮质激素、促性腺激素和催乳素分泌活性分析 可卡因滥用和可卡因戒除将提供荷尔蒙的指标 损害和恢复能力。下丘脑的刺激性测试- 垂体-性腺和肾上腺功能将被用来研究 可卡因的生殖系统毒性。 新药减毒效果的对照研究 还提出了灵长类动物模型中的自我管理。女性和 将对男性进行研究，以评估可能的性别差异 药物治疗。已建立的可操作性行为程序将 可用于评价新药疗法的疗效和安全性 可卡因和海洛因自我给药。一种新的多药滥用模式将 被开发成同时模拟可卡因和海洛因(快球) 自治。新的药物疗法对“速球”的影响 将对自治进行评估。毒品歧视程序将 用来预测治疗效果和最佳剂量范围 新药。这些研究应该有助于新的临床试验 药物滥用治疗。

Cocaine abuse by young men and women is a major public health problem today. A wide spectrum of medical disorders are associated with cocaine abuse and dependence including reproductive dysfunction (hyperprolactinemia, amenorrhea, luteal phase defects, male impotence); pregnancy abnormalities and impaired perinatal development; life threatening cerebrovascular and cardiovascular anomalies as well as compromised immune function which increases risk for infectious disease including AIDS. The proposed continuation of our NIDA Clinical Research Center, "Polydrug Abuse in Women" focuses upon the neuroendocrine consequences of cocaine abuse as well as the pre-clinical evaluation of new medications for treatment of cocaine abuse and polydrug abuse. Possible gender differences in vulnerability to cocaine's adverse biologic consequences will be assessed by inclusion of both male and female subjects. Scientific and congressional concerns have recently converged to emphasize the importance of studying women as well as men. We propose to conduct a parametric evaluation of the effects of chronic cocaine abuse and dependence on neuroendocrine hormones essential for normal reproductive function in parallel studies in women and in a primate model. Hyperprolactinemia is often associated with cocaine abuse and may compromise immune function. Cocaine stimulates adrenocorticotropin (ACTH) secretion which may subsequently modify immune function and susceptibility for infectious disease including AIDS. Computer-based pulse frequency analysis of ACTH, gonadotropin and prolactin secretory activity during cocaine abuse and cocaine abstinence will provide an index of hormonal impairment and capacity for recovery. Provocative tests of hypothalamic- pituitary-gonadal and adrenal function will be used to study the sites of cocaine's reproductive system toxicity. Controlled studies of the effectiveness of new medications in reducing drug self-administration in the primate model are also proposed. Females and males will be studied to assess possible gender differences in response to pharmacotherapy treatment. Established operant behavioral procedures will be used to evaluate the efficacy and safety of new pharmacotherapies on cocaine and heroin self-administration. A new model of polydrug abuse will be developed to simulate simultaneous cocaine and heroin ("speedball") self-administration. The effects of new pharmacotherapies on "speedball" self-administration will be evaluated. Drug discrimination procedures will be used to predict the therapeutic efficacy and the optimal dose range of new medications. These studies should facilitate clinical trials of new drug abuse treatments.