Candidate. The candidate, Heather M. Haughey, Ph.D., is a research associate with extensive experience in both neurochemical and molecular, approaches to the study of alcohol dependence but little experience with clinical approaches and research with humans. Her immediate career goal is to acquire the research and professional skills necessary for achieving her long-term goal of developing an independent, extramurally-funded translational research that spans molecular, cellular, and behavioral approaches to the study of alcohol dependence in humans. A five-year Career Development Plan will provide the candidate with the multi-disciplinary skills required to ultimately lead an independent and highly productive research program in alcohol dependence. Career Development Plan. This plan has been carefully devised to satisfy specific career development needs in the following major areas: (1) clinical research methods in alcohol dependence;(2) instrumentation and analysis of genotyping single nucleotide polymorphisms;and (3) quantitative skills and biostatistics. Formal training in these highly specialized areas will be achieved through an intensive curriculum of seminars, classes, tutorials, extramural didactics, and research studies. Environment. The environment for Dr. Haughey's proposed training is outstanding. The primary sponsor, Dr. Kent Hutchison, is a well-established extramurally funded scientist with an excellent record of successful mentoring and a decade of experience in human alcohol research;the co-sponsors and consulting mentors provide excellent guidance in specific components of the research plan, including molecular biology, genetics and statistical methodologies. Research. Three specific aims are proposed which seek to test the overall global hypothesis that polymorphisms within the NET gene that alter function/expression contribute to the development of alcoholism. We propose 1) to determine the functional significance of NET coding SNPs at a cellular level;2) to identify and characterize gene-bypharmacotherapy interaction(s) on intermediate laboratory based phenotypes (e.g., cue elicited craving, sensitivity to the acute effects of alcohol);and 3) to conduct secondary analyses of existing datasets (e.g., WHO/ISBRA) to determine whether variation in the NET gene is associated with the presence of alcohol dependence and/or depression. The findings from these studies will offer insight into the genetic determinants influencing the development of alcoholism and may guide the development of more effective pharmacotherapies for these devastating brain disorders.