Pharmacopsychiatry 2008; 41: S89-S98
DOI: 10.1055/s-2008-1080936
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

A Mathematical Model of Presynaptic Dopamine Homeostasis: Implications for Schizophrenia

Z. Qi 1 , 2 , 3 , 4 , G. W. Miller 2 , 3 , E. O. Voit 1 , 4
  • 1Department of Biomedical Engineering, Georgia Institute of Technology and Emory University Medical School, Atlanta, GA, USA
  • 2Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
  • 3Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA
  • 4Integrative BioSystems Institute, Georgia Institute of Technology, Atlanta, GA, USA
Further Information

Publication History

Publication Date:
28 August 2008 (online)

Abstract

Several lines of evidence implicate altered dopamine neurotransmission in schizophrenia. Current drugs for schizophrenia focus on postsynaptic sites of the dopamine signaling pathways, but do not target presynaptic dopamine metabolism. We have begun to develop a mathematical model of dopamine homeostasis, which will aid our understanding of how genetic, environmental, and pharmacological factors alter the functioning of the presynaptic dopamine neuron. Formulated within the modeling framework of Biochemical Systems Theory, the mathematical model integrates relevant metabolites, enzymes, transporters, and regulators involved in the control of the biochemical environment within the dopamine neuron. In this report we use the model to assess several components and factors that affect the dopamine neuron and have been implicated in schizophrenia. These include the enzymes COMT, MAO, and TH, different dopamine transporters, as well as administration of amphetamine or cocaine. We also investigate scenarios that could increase (or decrease) dopamine neurotransmission and thus exacerbate (or alleviate) symptoms of schizophrenia. Our results indicate that the model predicts the effects of various factors related to schizophrenia on the homeostasis of the presynaptic dopamine neuron rather well. Upon further refinements and testing, the model has the potential of serving as a tool for screening novel therapeutics aimed at altering presynaptic dopamine function and thereby potentially ameliorating some of the symptomology of schizophrenia.

References

Correspondence

E. O. Voit, PhD 

Department of Biomedical Engineering

Georgia Institute of Technology and Emory

University Medical School

313 Ferst Drive

Suite 4103

Atlanta

GA 30332-0535

USA

Email: eberhard.voit@bme.gatech.edu