Anxiolytic Effects and Abuse of BZ Receptor Ligands

BZ 受体配体的抗焦虑作用和滥用

基本信息

批准号：
7810105
负责人：
JAMES K ROWLETT
金额：
$ 34.7万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7810105
关键词：
Adverse effects American Anti-Anxiety Agents Anticonvulsants Anxiety Area Benzodiazepine Receptor Benzodiazepines Biological Assay Brain Characteristics Contracts Data Dependence Diazepam Drug Prescriptions Drug abuse Elderly Employment Endocrine Equipment Fee-for-Service Plans Female Funding Gender Goals Gonadal Steroid Hormones High Prevalence Knowledge Laboratories Laboratory Study Ligands Luteal Phase Maintenance Measures Menstrual cycle Mental disorders Modeling Modern Medicine Monitor Monkeys Muscle relaxants National Institute of Drug Abuse Occupations Oregon Ovarian Cycles Pharmaceutical Preparations Physical Dependence Physiological Plasma Play Positioning Attribute Postdoctoral Fellow Preparation Primates Procedures Process Progesterone Psychotropic Drugs Recovery Relative (related person)Research Research Project Grants Research Support Role Sampling Schedule Self Administration Services Sex Characteristics Sleep Disorders Swab Technology Therapeutic Time United States National Institutes of Health Vagina Woman Work base drug of abuse experience gamma-Aminobutyric Acid hypnotic insight male men neurosteroids nonhuman primate parent grant patient population programs public health relevance receptor research study sex

项目摘要

DESCRIPTION (provided by applicant): This application is a Competitive Revision, as described in Notice Number NOT-OD-058, entitled "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". The parent grant is R01DA017792-10, "Anxiolytic Effects and Abuse of BZ Receptor Ligands". The overall goal of the parent grant is to investigate the extent to which GABAA receptor subtypes are differentially involved in the anxiolytic effects, self-administration, and physical dependence associated with benzodiazepine (BZ) ligands, using relevant nonhuman primate models. The revised component of this application is to evaluate potential sex differences and menstrual cycle effects in BZ self-administration. In patient populations, women are associated with higher rates of BZ use and abuse, which we hypothesize to involve, in part, enhanced reinforcing effects of these ligands by sex hormones and their neuroactive steroid metabolites. Under the parent grant, reinforcing effects are evaluated using progressive-ratio schedules of i.v. drug self-administration, and we are requesting a revision to include experiments with both female and male monkeys. Identification of potential sex differences and menstrual cycle effects on the self-administration of BZ ligands will provide fundamental information for understanding gender-related differences in the abuse potential of these drugs that, in turn, should aid in developing safer and more broadly effective anti-anxiety medications. PUBLIC HEALTH RELEVANCE: Valium and related drugs, referred to as "benzodiazepines" are prescribed widely for the treatment of anxiety and sleep disorders, two of the most common psychiatric disorders in the U.S. Benzodiazepines are considered to be among the safest prescription drugs in modern medicine, but they unfortunately are also drugs of abuse, with higher prevalence in women than men. The aim of this revision to our parent grant is to uncover sex differences in the abuse potential of benzodiazepines, with the overall goal of developing safer drugs for treating anxiety and sleep disorders regardless of gender.

描述（由申请人提供）：本申请是竞争性修订，如通知号 NOT-OD-058 中所述，标题为“NIH 宣布恢复法案资金用于竞争性修订申请的可用性”。母基金是 R01DA017792-10，“BZ 受体配体的抗焦虑作用和滥用”。母基金的总体目标是使用相关的非人类灵长类动物模型，研究 GABAA 受体亚型在与苯二氮卓 (BZ) 配体相关的抗焦虑作用、自我给药和身体依赖性中的差异程度。该应用程序的修订部分是评估 BZ 自我给药中潜在的性别差异和月经周期影响。在患者群体中，女性与 BZ 使用和滥用率较高有关，我们推测这在一定程度上与性激素及其神经活性类固醇代谢物对这些配体的增强作用有关。在母基金的资助下，强化效果是使用 i.v. 的渐进比例表来评估的。药物自我给药，我们请求修订以包括雌性和雄性猴子的实验。识别潜在的性别差异和月经周期对 BZ 配体自我给药的影响将为了解这些药物滥用潜力中的性别相关差异提供基本信息，从而有助于开发更安全、更广泛有效的抗-BZ 配体。焦虑药物。公共健康相关性：安定及相关药物（称为“苯二氮卓类药物”）广泛用于治疗焦虑和睡眠障碍，这是美国最常见的两种精神疾病。苯二氮卓类药物被认为是现代医学中最安全的处方药之一。但不幸的是，它们也是滥用药物，女性的患病率高于男性。此次家长补助金修订的目的是揭示苯二氮卓类药物滥用潜力的性别差异，总体目标是开发更安全的药物来治疗焦虑和睡眠障碍，无论性别如何。