POLYDRUG ABUSE IN WOMEN: NIDA CLINICAL RESEARCH CENTER

女性滥用多种药物：NIDA 临床研究中心

• 批准号: 3105346
• 负责人: JACK H MENDELSON
• 金额: $ 118.52万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3105346
• 关键词: drug abuse; drug abuse chemotherapy; endocrine pharmacology; female; female reproductive system; reproductive system pharmacology

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.

青年男女滥用避孕药具是一个重大的公共卫生问题 今天 一系列的医学疾病都与可卡因有关 滥用和依赖，包括生殖功能障碍 （高催乳素血症、闭经、黄体功能不全、男性阳痿）; 妊娠异常和围产期发育受损;寿命 威胁性脑血管和心血管异常以及 免疫功能受损，增加感染性疾病的风险 包括艾滋病。 我们的NIDA临床研究的拟议继续 中心，“妇女多药滥用”的重点是神经内分泌 可卡因滥用的后果以及新药物的临床前评价 治疗可卡因滥用和多种药物滥用的药物。 可能 可卡因不良生物学效应的性别差异 将通过纳入男性和女性来评估结果 科目 科学界和国会的关注最近集中在 强调研究女性和男性的重要性。 我们建议进行一个参数评估的影响，慢性 可卡因的滥用和依赖对神经内分泌激素至关重要， 女性和灵长类动物平行研究中的正常生殖功能 模型 高催乳素血症通常与可卡因滥用有关， 损害免疫功能 皮质醇刺激促肾上腺皮质激素（ACTH） 分泌物，随后可能改变免疫功能和易感性 包括艾滋病在内的传染病。 基于计算机的脉冲频率 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断将提供一个指数的激素 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用于研究 可卡因的生殖系统毒性 新药在减少药物滥用方面的有效性的对照研究 还提出了灵长类动物模型中的自我给药。 女性和 将对男性进行研究，以评估对以下问题可能存在的性别差异： 药物治疗 既定的操作性行为程序将 用于评价新药物治疗的有效性和安全性， 可卡因和海洛因自我管理。 一种新的多种药物滥用模式将 被开发来模拟可卡因和海洛因的同时使用（“快球”） 自我管理。 新药物治疗对“速度球”的影响 将对自我管理进行评估。 毒品歧视程序将 用于预测治疗效果和最佳剂量范围 新药 这些研究将促进新的 药物滥用治疗