||Professor and Director of Foundational Sciences, School of Dentistry
Deputy Director, Utah Addiction Center
Neurobiology of Disease
Brain and Behavior
Neuropharmacology, neurochemistry and aminergic transporters
Some psychostimulants of abuse can cause persistent damage to dopaminergic and/or serotonergic neurons in rodents, non-human primates and humans. For example, methamphetamine administration causes persistent dopaminergic deficits that, in part, resemble deficits occurring in Parkinson's disease. Dr. Fleckenstein's laboratory investigates receptor-mediated and subcellular mechanisms contributing to these deficits. A particular focus of the laboratory involves investigating the effects of stimulants on monoaminergic transporters, both because of relevance to the neurotoxicity of stimulants, and because of the laboratory's ongoing interest in the abuse liability of these agents.
A variety of techniques are employed in Dr. Fleckenstein's laboratory including radioligand-binding, rotating disk electrode voltammetry, monoamine uptake assays, western blotting, and high performance liquid chromatography to assess alterations in monoaminergic neuronal function after both non-contingent, and more recently, contingent drug administration.
Several research projects are ongoing in Dr. Fleckenstein's laboratory. One involves investigating mechanisms underlying the neurotoxic effects of methamphetamine, with a particular emphasis on the role of aging (e.g., the impact of the transition from adolescence to young adulthood) in this process. Another project involves investigating mechanisms underlying, and the functional consequences of, stimulant-induced vesicular trafficking. A third project involves assessing the identity and functional relevance of high molecular weight plasmalemmal dopamine transporter complexes that form after methamphetamine treatment. A forth involves investigating the impact of methamphetamine self-administration on both acute and long-term changes in monoaminergic neuronal function.
German, C.L., Hoonakker, A.J., Fleckenstein, A.E., and Hanson, G.R. (2014) Mephedrone alters basal ganglia and limbic neurotensin system. J Neurochem, (in press).
McFadden, L.M., Vieira-Brock, P.L., Hanson, G.R., and Fleckenstein, A.E. (2014) Methamphetamine self-administration attenuates hippocampal serotonergic deficits: Role of brain derived neurotrophic factor. Int J Neuropharmacol, (in press).
Baladi, M.G., Newman, A.H., Nielsen, S.M., Hanson, G.R., and Fleckenstein, A.E. (2014) Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia. Eur J Pharmacol, (in press).
Vieira-Brock, P.L., Nielsen, S.M., Andrenyak, D.M., Fleckenstein, A.E., and Wilkins, D.G. (2013) Age-related differences in the disposition of nicotine and cotinine in rat brain and plasma. Nicotine Tobacco Research, 15:1839–1848.
McFadden, L.M., Hanson, G.R., and Fleckenstein, A.E. (2013) The effects of methamphetamine self-administration on cortical monoaminergic deficits Induced by subsequent high-dose methamphetamine administrations. Synapse, 67:875-871.
Charntikov, S., Swalve, N., Pittenger, S., Fink, K., Schepers, S., Hu, G., Hadlock, G.C., Fleckenstein, A.E., Li, M., and Bevins, R.A. (2013) Assessment of iptakalim in preclinical models of nicotine abuse liability. Neuropharmacol, 75:138-144.
German, C.L., Hanson, G.R., and Fleckenstein, A.E. (2012) Amphetamine and methamphetamine reduce striatal dopamine transporter function without concurrent dopamine transporter relocalization. J Neurochem, 123:288-297.
McFadden, L.M., Hunt, M., Allen, S.C., Nielsen, S.M., Hanson, G.R., and Fleckenstein, A.E. (2012) Prior methamphetamine self-administration attenuates persistent serotonergic deficits induced by subsequent high-dose methamphetamine exposure. Drug and Alcohol Dependence, 126:87-94.
McFadden, L.M., Stout, K.A., Vieira-Brock, P.L., Allen, S.C., Nielsen, S.M., Wilkins, D.G., Hanson, G.R., and Fleckenstein, A.E. (2012) Methamphetamine self-administration causes acute decreases in monoaminergic transporter function. Synapse, 66:240-245.
McFadden, L.M., Hadlock, G.C., Allen, S.C., Brock, P.L., Stout, K.A., Wilkins, D.G., Hanson, G.R., and Fleckenstein, A.E. (2012) Methamphetamine self-administration leads to persistent striatal neuroadaptations and protection against subsequent methamphetamine exposure. J. Pharmacol. Exp. Ther., 340:295-303.