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: 7360561
• 负责人: Shanna Babalonis
• 金额: $ 5.39万
• 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 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7360561
• 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）：从许多方面积累的证据表明，性别在药物滥用中起着关键作用。生物因素，包括性腺性激素，对药物滥用方面的性别差异有重要影响，但尚未完全了解。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受体功能受到孕酮和许多镇静药物（包括苯二氮卓类）的积极调节。临床前体外和体内研究以及一些临床研究的证据表明，孕酮及其代谢产物可能会增强苯二氮卓类药物的行为效应。第一项拟议研究将采用受试者内设计，以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 mg/70 kg）对低循环性激素条件下健康绝经前妇女的主观、精神和生理影响的单独和联合作用。第二项研究，也是一个受试者内设计，将检查孕激素预处理对三唑仑（0.00，0.06，0.12和0.25 mg/70 kg）在健康绝经前妇女中的辨别刺激作用的影响，也是在低循环性激素的条件下。待测试的孕酮剂量将基于初始研究的结果（即，单独无活性的剂量，其产生最强的三唑仑作用增强）。这项研究将有助于阐明卵巢激素孕酮调节镇静药物三唑仑行为效应的方式。此外，这些研究将为旨在进一步阐明与苯二氮卓类药物作用的孕酮调节相关的机制的其他研究奠定基础，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不同性别的干预和/或预防战略以及健康管理办法。