Cocaine Sensitization & Dopamine Transporter Regulation

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DESCRIPTION: (Provided by Applicant): This new application for a "K05 Senior Scientist Award" from NIDA requests 5 years of support for Nancy R. Zahniser, Ph.D., Professor of Pharmacology, University of Colorado School of Medicine. The Department of Pharmacology is distinguished by its strengths in neuropharmacology, alcohol and drug abuse research; strong funding record; scientific impact; and collaborative atmosphere. Dr. Zahniser has had a NIDA "K02 Independent Scientist Award" for the past 9 years, and this support has been crucial to her career, allowing her not only to focus on drug abuse research but also to expand the scope of her research. For example, her early work suggested that the dopamine transporter (DAT) contributes to persistent expression of cocaine-induced behavioral sensitization. She helped to develop new electrochemical recording technology to measure concurrently DA clearance, a measure of in vivo DAT activity, and behavior in freely-moving rats. She and her graduate student have now used this method to confirm this relationship. Thus, only rats that showed cocaine-induced changes in DAT also exhibited behavioral sensitization. Development of this technology was instrumental in her recently receiving a MERIT Award to support her work. These results have lead to her long-term goal of understanding DAT regulation in the brain. She has identified membrane potential, protein kinases, DA D2 receptors and substrates as regulating DAT activity and expression. Her results, like those from other labs, suggest that DAT regulation occurs largely via changes in cell surface expression. Thus, she initiated a collaboration with Dr. Alexander Sorkin to study the basic molecular machinery and protein-protein interactions that occur during endocytic DAT trafficking in model cell systems and neuronal preparations. This K05 Award will provide her "protected time" to focus on this new direction, as well as on new projects studying DAT expression/function in stem cells and in cocaine-sensitive and -insensitive mice, all of which will significantly contribute to her career development and the drug abuse field. One of the most important and unique aspects of her work is the desire and ability to test hypotheses about DAT, derived from model systems, back in the brain. Dr. Zahniser has also consistently contributed to the drug abuse field by reviewing grants/manuscripts, serving on advisory panels and organizing symposia/meetings. She is active in training. Six of her 14 former graduate students and postdoctoral fellows are now doing drug abuse/alcohol research as independent faculty investigators. All 5 of her current trainees are working on drug abuse/alcohol research projects.