This application for a K05 Senior Scientist Award requests an additional 5 years of support from NIDA for Nancy Zahniser, Ph.D., Professor of Pharmacology and Neuroscience, U Colorado School of Medicine. The U Colorado is distinguished by its strong drug/alcohol addiction research, funding record, training programs and collaborative atmosphere. Dr. Zahniser's support by a NIDA K05 Award for the past 4 years has been crucial in allowing her to focus on and expand the scope of her drug addiction research. Her research seeks to understand how the differential initial behavioral responsiveness of individual rats to cocaine predicts their vulnerability to addiction, how the dopamine transporter (DAT) contributes to these phenotypes and how functional DAT expression is regulated. Recently, she began a new collaboration with Dr. Richard Allen that has enhanced her lab's behavioral testing repertoire to include conditioned place preference (CPP) and, very soon, self-administration. Overall, her work has shown that the initial locomotor response to cocaine can predict the extent of cocaine-induced locomotor sensitization and CPP, suggesting that factors like DAT that contribute to the different phenotypes may help to explain individual differences in reward. Such findings have sparked her interest in understanding how DAT is regulated and her productive collaboration with Dr. Alexander Sorkin. DAT regulation occurs largely via altered trafficking and cell surface expression. Their work has resulted in novel insights about the cellular mechanisms utilized during endocytic DAT trafficking in model cell systems. They are currently extending these findings to brain preparations. The ability to test hypotheses about DAT derived in model systems, back in the brain, remains one of the most important and unique aspects of Dr. Zahniser's work. Continued K05 support will provide her protected time to focus on new research directions and mentoring, as well as to utilize her recent leadership training in organizing a new university-wide drug addiction research center, integrating basic, clinical and treatment research. Dr. Zahniser contributed/s to NIDA's mission by serving on NIDA Council and IRP Board of Scientific Counselors, external advisory boards for other addiction centers, and as a reviewer. She is active in mentoring students, postdoctoral fellows and junior faculty who are supported by NIDA. Ten of her 20 former trainees are faculty members/senior fellows who continue independently to focus on drug/alcohol addiction research. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA015050-07
Application #
7392339
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Pilotte, Nancy S
Project Start
2002-05-01
Project End
2012-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
7
Fiscal Year
2008
Total Cost
$125,388
Indirect Cost
Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Rorabaugh, J M; Stratford, J M; Zahniser, N R (2015) Differences in bingeing behavior and cocaine reward following intermittent access to sucrose, glucose or fructose solutions. Neuroscience 301:213-20
Mandt, Bruce H; Copenhagen, Leland I; Zahniser, Nancy R et al. (2015) Escalation of cocaine consumption in short and long access self-administration procedures. Drug Alcohol Depend 149:166-72
Rorabaugh, Jacki M; Stratford, Jennifer M; Zahniser, Nancy R (2014) A relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior. PLoS One 9:e95019
Rao, Anjali; Sorkin, Alexander; Zahniser, Nancy R (2013) Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness. Synapse 67:668-77
Yamamoto, Dorothy J; Nelson, Anna M; Mandt, Bruce H et al. (2013) Rats classified as low or high cocaine locomotor responders: a unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors. Neurosci Biobehav Rev 37:1738-53
Simmons, Diana L; Mandt, Bruce H; Ng, Christopher M C et al. (2013) Low- and high-cocaine locomotor responding rats differ in reinstatement of cocaine seeking and striatal mGluR5 protein expression. Neuropharmacology 75:347-55
Yamamoto, Dorothy J; Zahniser, Nancy R (2012) Differences in rat dorsal striatal NMDA and AMPA receptors following acute and repeated cocaine-induced locomotor activation. PLoS One 7:e37673
Liu, Xinjian; Li, Fang; Stubblefield, Elizabeth A et al. (2012) Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res 22:321-32
Mandt, Bruce H; Johnston, Nickie L; Zahniser, Nancy R et al. (2012) Acquisition of cocaine self-administration in male Sprague-Dawley rats: effects of cocaine dose but not initial locomotor response to cocaine. Psychopharmacology (Berl) 219:1089-97
Rao, Anjali; Richards, Toni L; Simmons, Diana et al. (2012) Epitope-tagged dopamine transporter knock-in mice reveal rapid endocytic trafficking and filopodia targeting of the transporter in dopaminergic axons. FASEB J 26:1921-33

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