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DOI: 10.1055/s-2008-1080936
© Georg Thieme Verlag KG Stuttgart · New York
A Mathematical Model of Presynaptic Dopamine Homeostasis: Implications for Schizophrenia
Publication History
Publication Date:
28 August 2008 (online)
![](https://www.thieme-connect.de/media/pharmaco/2008S01/lookinside/thumbnails/10.1055-s-2008-1080936-1.jpg)
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.
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Correspondence
E. O. VoitPhD
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