Feedback model of extracellular dopamine concentration control

Dopamine is one of the central neurotransmitters; its homeostatic concentration is maintained through release, uptake, and feedback. The extracellular dopamine concentration is regulated presynaptically by the dopamine transporter (DAT) and dopamine autoreceptors. The postsynaptic control is mediated by postsynaptic dopamine receptors. Dopamine is the subject of a numerous experimental studies. As a result, great deal of experimental data describing the components of dopamine system has been collected. This experimental data provides an excellent foundation for theoretical study to model complex dopamine system. Mathematical modeling was based on published pharmacokinetic parameters for dopamine uptake and receptor binding in rat striatum. It was demonstrated computationally that both uptake by DAT and negative feedback mediated by receptors are necessary components to maintain a low extracellular dopamine concentration under basal conditions. The mathematical modeling also showed the critical role of negative feedback to control stable extracellular dopamine concentration under conditions of increased/decreased dopamine release.