Annette Fleckenstein
Professor of Pharmacology and Toxicology
Title: Professor of Pharmacology and Toxicology
Email address:
Education and Training:
- B.S. 1988, Western Michigan University
- M.S. 1990, Western Michigan University
- Ph.D. 1994, Michigan State University
- Postdoctoral Fellow 1994-1995, National Institutes of Health - National Institute on Drug Abuse, Add
Research Interests:
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.
Selected Publications:
- Fleckenstein, A.E., Volz, T.J., and Hanson, G.R. (2009) Psychostimulant-induced alterations in vesicular monoamine transporter-2 function: neurotoxic and therapeutic implications. Neuropharmacology, 56:133-138.
- Hanson, G.R. and Fleckenstein, A.E. (2009) Basic neuropharmacological mechanisms of methamphetamine. In: Methamphetamine Addiction: From Basic Science to Treatment. The Guilford Press, New York.
- Volz, T.J., Farnsworth, S.J., Hanson, G.R., and Fleckenstein, A.E. (2009) Measurement of plasmalemmal dopamine transport, and K+-stimulated dopamine release in frozen rat brain tissue. J Neurosci Methods, 180:317-320.
- Farnsworth, S.J., Volz, T.J., Hanson, G.R., and Fleckenstein, A.E. (2009) Cocaine alters vesicular dopamine sequestration and K+-stimulated release: Role of D2 receptor activation. J Pharmacol. Exp. Ther., 328:807-812.
- Volz, T.J., Farnsworth, S.J., Hanson, G.R., and Fleckenstein, A.E. (2009) Method development and validation of an in vitro model of the effects of methylphenidate on membrane-associated synaptic vesicles. J. Neurosci. Methods, 177:177-182.
- Hadlock, G.C., Baucum, A.J., King, J.L., Horner, K.A., Cook, G.A., Riordan, J.A., Gibb, J.W., Wilkins, D.G., Hanson, G.R., and Fleckenstein, A.E. (2009) Mechanisms underlying methamphetamine-induced dopamine transporter complex formation. J. Pharmacol. Exp. Ther., 329:169-174.
- Hanson, J.E., Birdsall, E., Sepherian, K.S., Crosby, M.A., Keefe, K.A., Gibb, J.W., Hanson, G.R., and Fleckenstein, A.E. (2009) Methamphetamine-induced dopaminergic deficits and refractoriness to subsequent treatment. Eur. J. Pharmacol., 607:68-73.
- Volz, T.J., Farnsworth, S.J., Hanson, G.R., and Fleckenstein, A.E. (2008) Methylphendiate-induced alterations in synaptic vesicle trafficking and activity: Functional consequences and therapeutic implications. Ann. N.Y. Acad. Sci., 1139:285-290.
- Volz, T.J., Farnsworth, S.J., Hanson, G.R., and Fleckenstein, A.E. (2008) Methylphenidate-induced increases in vesicular dopamine sequestration and dopamine release in the striatum: The role of muscarinic and dopamine D2 receptors. J. Pharmacol. Exp. Ther., 327:161-167.
- Volz, T.J., Farnsworth, S.J., Rowley, S.D., Hanson, G.R., and Fleckenstein, A.E. (2008) Age-dependent differences in dopamine transporter and vesicular monoamine transporter-2 function and implications for methamphetamine neurotoxicity. Synapse, 63:147-151.
- Chu, P.W., Seferian, K.S., Birdsall, E., Truong, J.G., Riordan, J.A., Metcalf, C.S., Hanson, G.R., and Fleckenstein, A.E. (2008) Differential regional effects of methamphetamine on dopamine transport. Eur. J. Pharmacol., 590:105-110.
