Mifepristone As A Pharmacological Intervention For Stress-Induced Alcohol Drinking

 描述（由申请人提供）：该指导研究科学家发展应用程序（K 01）将为Haass-Koffler博士提供技能和保护时间：1）开发研究计划，调查压力如何促进酒精的使用; 2）开发和测试针对酒精依赖个体的压力反应的药物。她的主要目标是获得密集的指导，这将帮助她成为一个强大的独立的翻译和临床研究人员的药理干预集中在减轻压力酗酒。该K 01将支持她的目标，以获得进行严格的临床研究所需的指导，知识和经验，包括：（1）获得药物治疗干预的专业知识，以防止酒精依赖个体的压力诱导消费;（2）获得人类酒精实验室研究的知识，以补充她的神经科学专业知识;（3）获得如何评估应激-神经内分泌通路以整合神经元和下丘脑-垂体-肾上腺轴（HPA）数据的经验;（4）学习进行重复测量分析。Haass-Koffler博士的培训将有助于她通过更好地理解以下内容来启动未来的酒精研究：（5）评估心理压力诱导方法以评估情绪结果;（6）评估遗传脆弱性在酒精使用障碍（AUD）发展中的作用;（7）在神经科学和人类实验室研究之间建立翻译交流，以启发酒精和压力研究的新途径和新假设的发展。职业发展计划包括与导师和合作者的结构化会议;统计学和心理学的研究生课程和研讨会;访问他们实验室的合作者（NIH，耶鲁大学和普罗维登斯VA医学中心）;参加基于网络的研讨会，以开发药代动力学/药效学（PK/PD）建模的高级培训;参加会议，与酒精研究社区互动。培训计划的重点是完成一项试点实验室研究，安慰剂对照试验，以评估米非司酮的效果（一种糖皮质激素受体拮抗剂，被研究为酒精依赖的潜在治疗药物）在育亨宾引发的应激诱导条件下（一种已知可诱导乙醇寻求行为恢复的α-2肾上腺素受体拮抗剂）与一系列酒精实验室疗程配对。

 DESCRIPTION (provided by applicant): This Mentored Research Scientist Development application (K01) will provide Dr. Haass-Koffler with the skills and protected time to: 1) develop a program of research investigating how stress facilitates the use of alcohol; and 2) develop and test medications that target the stress reaction in alcohol-dependent individuals. Her main objective is to obtain intensive mentoring that will help her to become a strong independent translational and clinical researcher of pharmacological interventions centered on stress reduction in alcoholism. This K01 will support her goals to gain the mentorship, knowledge and experience required to conduct rigorous clinical research including: (1) gain expertise in pharmacotherapy interventions to prevent stress-induced consumption in alcohol-dependent individuals; (2) gain knowledge in human alcohol laboratory research to complement her neuroscience expertise; (3) gain experience on how to evaluate the stress-neuroendocrine pathway to integrate neuronal and hypothalamic-pituitary-adrenal axis (HPA) data; and (4) learn to perform repeated measures analyses. With this K01, Dr. Haass-Koffler's training will assist her in initiating future alcohol research by gaining a better understanding of: (5) evaluating psychological stress-induction methodologies to assess emotional outcomes; (6) assessing the contribution of genetic vulnerability in the development of Alcohol Use Disorder (AUD); and (7) establishing translational communication between neuroscience and human laboratory studies to inspire new avenues and development of new hypotheses in alcohol and stress research. The career development plan includes structured meetings with mentors and collaborators; graduate level courses and seminars in statistics and psychology; visits to collaborators in their laboratories (NIH, Yale and Providence VA Medical Center); attending Web-based workshop to develop advanced training in Pharmacokinetics/Pharmacodynamics (PK/PD) modeling; attending conferences to interact with the alcohol research communities. The training program is focused on the completion of a pilot laboratory study consisting of a randomized, placebo-controlled trial to assess the effects of mifepristone (a glucocorticoid-receptor antagonist investigated as a potential therapeutic agent of alcohol dependence) in a stress-induced condition triggered by yohimbine (an a-2 adrenoceptor antagonist known to induce reinstatement of ethanol-seeking behaviors) paired to a series of alcohol laboratory sessions.