This is a Career Development Award proposal for Dr. Annette Fleckenstein. She is a Professor of Pharmacology and Toxicology at the University of Utah. She has been active in drug abuse research for 13 years and has made important contributions to elucidating the effects of psychostimulants on dopamine (DA) transporter (DAT) and vesicular monoamine transporter-2 ( /MAT-2) regulation and function, especially as related to the neurotoxic effects of the amphetamines. The applicant is a current K02 recipient, and this has permitted the applicant to dramatically decrease her institutional responsibilities and devote 75% of her time to research and professional development as described in her application. Renewal of this award is requested so that the applicant can continue directing research which test the hypotheses that: 1) methamphetamine (METH)-induced DAT complex formation is associated with, and may contribute to, the dopaminergic deficits caused by the stimulant;2) methylphenidate uniquely affects monoaminergic vesicular function and distribution by a mechanism that includes novel shifts in VMAT-2M-mediated DA transport kinetics;and 3) "latter-stage events" related to intracellular DA management are critical for the persistent dopaminergic deficits caused by METH, and that these events are absent in both adolescent rats and those treated with METH during development. Continued support of this K02 award will not only allow the applicant to expand upon these studies, but also develop expertise in technologies new to her laboratory. In particular, funding of the K02 will facilitate the incorporation of self-administration technology into her laboratory that will permit investigation as to whether transporters are altered in that clinically relevant paradigm. Further, renewal of the K02 will allow the applicant to continue and expand interdisciplinary collaborative efforts with researchers both within and outside of the University of Utah as delineated in the proposal.

Public Health Relevance

Psychostimulant abuse is a significant public health issue. The vesicular monoamine transporter-2 and the dopamine transporter are principal targets of these agents. Accordingly, support for this K02 award will provide support to allow the applicant to study the impact of stimulants such as methamphetamine, cocaine and methylphenidate on transporter function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA019447-08
Application #
8247059
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Frankenheim, Jerry
Project Start
2005-04-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
8
Fiscal Year
2012
Total Cost
$132,192
Indirect Cost
$9,792
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Baladi, Michelle G; Newman, Amy H; Nielsen, Shannon M et al. (2014) Dopamine D(3) receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: role of hyperthermia. Eur J Pharmacol 732:105-10
Charntikov, S; Swalve, N; Pittenger, S et al. (2013) Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine. Neuropharmacology 75:138-44
McFadden, Lisa M; Hanson, Glen R; Fleckenstein, Annette E (2013) The effects of methamphetamine self-administration on cortical monoaminergic deficits induced by subsequent high-dose methamphetamine administrations. Synapse 67:875-81
Vieira-Brock, Paula L; Andrenyak, David M; Nielsen, Shannon M et al. (2013) Age-related differences in the disposition of nicotine and metabolites in rat brain and plasma. Nicotine Tob Res 15:1839-48
McFadden, Lisa M; Hadlock, Greg C; Allen, Scott C et al. (2012) Methamphetamine self-administration causes persistent striatal dopaminergic alterations and mitigates the deficits caused by a subsequent methamphetamine exposure. J Pharmacol Exp Ther 340:295-303
Hanson, G R; Hoonakker, A J; Alburges, M E et al. (2012) Response of limbic neurotensin systems to methamphetamine self-administration. Neuroscience 203:99-107

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