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.
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.
|German, Christopher L; Gudheti, Manasa V; Fleckenstein, Annette E et al. (2017) Brain Slice Staining and Preparation for Three-Dimensional Super-Resolution Microscopy. Methods Mol Biol 1663:153-162|
|Fricks-Gleason, Ashley N; German, Christopher L; Hoonakker, Amanda J et al. (2016) An acute, epitope-specific modification in the dopamine transporter associated with methamphetamine-induced neurotoxicity. Synapse 70:139-46|
|German, Christopher L; Baladi, Michelle G; McFadden, Lisa M et al. (2015) Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease. Pharmacol Rev 67:1005-24|
|Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M et al. (2015) Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits. J Pharmacol Exp Ther 355:463-72|
|Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M et al. (2015) Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits. Int J Neuropsychopharmacol 18:|
|McFadden, Lisa M; Vieira-Brock, Paula L; Hanson, Glen R et al. (2015) Prior methamphetamine self-administration attenuates the dopaminergic deficits caused by a subsequent methamphetamine exposure. Neuropharmacology 93:146-54|
|German, Christopher L; Fleckenstein, Annette E; Hanson, Glen R (2014) Bath salts and synthetic cathinones: an emerging designer drug phenomenon. Life Sci 97:2-8|
|Baladi, Michelle G; Nielsen, Shannon M; Umpierre, Anthony et al. (2014) Prior methylphenidate self-administration alters the subsequent reinforcing effects of methamphetamine in rats. Behav Pharmacol 25:758-65|
|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|
|McFadden, Lisa M; Vieira-Brock, Paula L; Hanson, Glen R et al. (2014) Methamphetamine self-administration attenuates hippocampal serotonergic deficits: role of brain-derived neurotrophic factor. Int J Neuropsychopharmacol 17:1315-20|
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