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.
Stressful events evoke a series of physiological and emotional responses that typically facilitate adaptation to or coping with the events. However, when intense or prolonged, stress can lead to a wide range of health and psychiatric illnesses, including alcohol use disorders (AUD). In spite of the importance of stress to the development of alcoholism, no currently approved medications target stress-related systems.
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