This is a Senior Scientist Award proposal for Dr. Glen R. Hanson. Dr. Hanson is a tenured professor in the Department of Pharmacology and Toxicology at the University of Utah. He has been active in drug abuse research for over 15 years and has made important contributions to elucidating: (a) the role of dopamine systems in neurotoxicity caused by amphetamine analogs; (b) the role of reactive oxygen species in mediating monoaminergic changes caused by amphetamine analogs; (c) the influence of the stimulants of abuse on neuropeptide systems; (d) the role of dopamine receptor subtypes in the regulation of extrapyrarnidal and limbic neuropeptide systems. Dr. Hanson currently devotes 40-50% of his time to research and student mentoring while 50-60% of his effort is occupied by teaching, departmental and college responsibilities. This Senior Scientist Award will allow Dr. Hanson to increase his research effort to approximately 80%. During the time of support by this award, he will direct research which tests the following principal hypotheses: (a) the generation of dopamine-related reactive oxygen species is a major contributor to the neurochemical deficits occurring in the striatal monoaminergic systems after high doses of methamphetamine (METH); (b) methcathinone, a relatively new designer amphetamine, exerts profound short-and long-term effects on extrapyramidal and limbic monoaminergic systems and has significant neurotoxic potential; (c) METH acutely and selectively alters the nature and function of the dopamine transporter in a reversible manner; (d) low and high doses of METH preferentially influence the indirect (striatal-pallidal) and direct (striatal-nigral) efferent pathways to the basal ganglia output nuclei, respectively; (e) changes in neuropeptide systems occur in humans exposed to the potent stimulants of abuse much like that observed in rats after treatment with these same drugs. The increase in research time resulting from a Senior Scientist Award will allow Dr. Hanson to develop expertise in technologies new to his laboratory required to test these hypotheses, such as: (a) free radical analysis; (b) transporter function and ligand assays; (c) in situ hybridization for neuropeptide precursor mRNA. This award will help Dr. Hanson to mentor more effectively inexperienced researchers at the undergraduate, graduate, postdoctoral and young faculty levels as these developing scientists mature and establish themselves in neuroscience research in general, and drug abuse research in particular. In addition, as a mentor Dr. Hanson will be especially supportive of the involvement of underrepresented minorities in drug abuse research.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA000378-03
Application #
6175078
Study Section
Special Emphasis Panel (ZDA1-MXS-M (01))
Program Officer
Frankenheim, Jerry
Project Start
1998-08-01
Project End
2007-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
3
Fiscal Year
2003
Total Cost
$129,422
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Baladi, Michelle G; Nielsen, Shannon M; McIntosh, J Michael et al. (2016) Prior nicotine self-administration attenuates subsequent dopaminergic deficits of methamphetamine in rats: role of nicotinic acetylcholine receptors. Behav Pharmacol 27:422-30
Alburges, Mario E; Hoonakker, Amanda J; Cordova, Nathaniel M et al. (2015) Effect of low doses of methamphetamine on rat limbic-related neurotensin systems. Synapse 69:396-404
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
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
Alburges, Mario E; Hoonakker, Amanda J; Cordova, Nathaniel M et al. (2014) Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine. Psychopharmacology (Berl) 231:2933-40
German, Christopher L; Hoonakker, Amanda H; Fleckenstein, Annette E et al. (2014) Mephedrone alters basal ganglia and limbic neurotensin systems. J Neurochem 130:402-7
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
McFadden, Lisa M; Stout, Kristen A; Vieira-Brock, Paula L et al. (2012) Methamphetamine self-administration acutely decreases monoaminergic transporter function. Synapse 66:240-5

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