Anxiolytic Effects and Abuse of BZ Receptor Ligands

描述（由申请人提供）：该申请是竞争性修订，如编号no - od -058通知所述，题为“NIH宣布竞争性修订申请的恢复法案资金可用性”。父母批准号为R01DA017792-10，“BZ受体配体的抗焦虑作用和滥用”。本研究的总体目标是利用相关的非人灵长类动物模型，研究GABAA受体亚型在苯二氮卓类药物（BZ）配体相关的抗焦虑作用、自我给药和身体依赖中的差异程度。本应用程序的修订部分是评估BZ自我给药的潜在性别差异和月经周期影响。在患者群体中，女性使用和滥用BZ的比例较高，我们假设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。在父母资助下，强化效果是使用静脉注射药物自我给药的渐进比例时间表来评估的，我们正在要求修改，以包括雌性和雄性猴子的实验。确定潜在的性别差异和月经周期对BZ配体自我给药的影响，将为理解这些药物滥用潜力中的性别相关差异提供基础信息，进而有助于开发更安全、更有效的抗焦虑药物。

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.