Separate and Combined Effects of Progesterone and Triazolam in Healthy Women

黄体酮和三唑仑对健康女性的单独和联合作用

• 批准号: 7501380
• 负责人: Shanna Babalonis
• 金额: $ 5.28万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7501380
• 关键词: Adult; Affect; Behavioral; Benzodiazepines; Biological; Biological Factors; Blood; Cardiovascular system; Chemosensitization; Clinical Research; Condition; Dependence; Development; Dose; Drug Modulation; Drug abuse; Estradiol; Female; Foundations; Gender; Gonadal Steroid Hormones; Health; Health behavior; Hormonal; Hormones; In Vitro; Individual; Intervention; Mediating; Menstrual cycle; Nervous System Physiology; Neuraxis; Neurons; Oral; Ovarian Steroid Hormone; Ovarian hormone; Peripheral Nervous System; Pharmaceutical Preparations; Phase; Physiological; Plasma; Play; Premenopause; Prevention; Prevention strategy; Progesterone; Psychomotor Performance; Psychotropic Drugs; Purpose; Range; Reproductive Health; Research Design; Role; Sex Characteristics; Steroids; Stimulus; Testing; Time; Triazolam; Woman; base; design; drug of abuse; in vivo; men; non-genomic; pre-clinical; receptor; receptor function; sedative; steroid hormone

DESCRIPTION (provided by applicant): There is accumulating evidence from many directions indicating that gender plays a critical role in drug abuse. Biological factors, including gonadal sex hormones, contribute in a significant although incompletely understood manner, to gender differences in drug abuse. Female sex hormones have been shown to affect central nervous system function and modulate the effects of drugs of abuse. For example, GABAA receptor function is positively modulated by both progesterone and many sedative drugs, including the benzodiazepines. There is evidence from preclinical in vitro and in vivo studies as well as some clinical research suggesting that progesterone and its metabolites may enhance the behavioral effects of benzodiazepines. The first proposed study will utilize a within-subject design to examine the separate and combined effects of a range of doses of micronized sublingual progesterone (0, 50, 150 and 250) and oral triazolam (0.00, 0.12 and 0.25 mg/70 kg) on the subjective, psychomotor and physiological effects of healthy premenopausal women under conditions of low circulating sex hormones. The second study, also a withinsubject design, will examine the effect of progesterone pretreatment on the discriminative stimulus effects of triazolam (0.00, 0.06, 0.12 and 0.25 mg/70 kg) in healthy, premenopausal women, also under conditions of low circulating sex hormones. The progesterone dose to be tested will be determined based on the results of the initial study (i.e., the dose, inactive in isolation, that engenders the most robust potentiation of triazolam effects). The proposed studies will help to clarify the manner in which the ovarian hormone progesterone modulates the behavioral effects of the sedative drug triazolam. In addition, these studies will establish a foundation for additional studies designed to further elucidate mechanisms associated with progesterone modulation of benzodiazepine effects, thereby further informing gender differences in health and behavior. As such, these studies will contribute towards the development of gender-specific intervention and/or prevention strategies and health management approaches.

描述（由申请人提供）：来自多个方向的越来越多的证据表明，性别在药物滥用中起着至关重要的作用。包括性激素在内的生物因素以一种显着但尚不完全了解的方式对药物滥用的性别差异产生影响。女性性激素已被证明会影响中枢神经系统功能并调节滥用药物的影响。例如，GABAA 受体功能受到黄体酮和许多镇静药物（包括苯二氮卓类药物）的正向调节。临床前体外和体内研究以及一些临床研究的证据表明，黄体酮及其代谢物可能会增强苯二氮卓类药物的行为效应。第一项拟议研究将利用受试者内设计来检查一系列剂量的微粉化舌下黄体酮（0、50、150和250）和口服三唑仑（0.00、0.12和0.25毫克/70公斤）的单独和组合效果对健康绝经前妇女在低循环性激素条件下的主观、精神运动和生理影响。第二项研究也是受试者内设计，将检查黄体酮预处理对健康绝经前女性（也是在低循环性激素条件下）三唑仑（0.00、0.06、0.12 和 0.25 毫克/70 公斤）的辨别刺激效果的影响。待测试的黄体酮剂量将根据初始研究的结果确定（即，单独无活性时产生最强烈的三唑仑效应增强的剂量）。拟议的研究将有助于阐明卵巢激素黄体酮调节镇静药物三唑仑行为影响的方式。此外，这些研究将为其他研究奠定基础，旨在进一步阐明与黄体酮调节苯二氮卓类作用相关的机制，从而进一步了解健康和行为方面的性别差异。因此，这些研究将有助于制定针对性别的干预和/或预防策略以及健康管理方法。