Toward Precise Modeling of Dopamine Release Kinetics: Comparison and Validation of Kinetic Models Using Voltammetry.

Dopamine (DA) is a neurotransmitter present within the animal brain that is responsible for a wide range of physiologic functions, including motivation, reward, and movement control. Changes or dysfunction in the dynamics of DA release are thought to play a pivotal role in regulating various physiological and behavioral processes, as well as leading to neuropsychiatric diseases. Therefore, it is of fundamental interest to neuroscientists to understand and accurately model the kinetics that govern dopaminergic neurotransmission. In the past several decades, many mathematical models have been proposed to attempt to capture the biologic parameters that govern dopaminergic kinetics, with each model seeking to improve upon a previous model. In this review, each of these models are derived, and the ability of each model to properly fit two fast-scan cyclic voltammetry (FSCV) data sets will be demonstrated and discussed. The dopamine oxidation current in both FSCV data sets exhibits hang-up and overshoot behaviors, which have traditionally been difficult for mathematical models to capture. We show that more recent models are better able to model DA release that exhibits these behaviors but that no single model is clearly the best. Rather, models should be selected based on their mathematical properties to best fit the FSCV data one is trying to model. Developing such differential equation models to describe the kinetics of DA release from the synapse confers significant applications both for advancing scientific understanding of DA neurotransmission and for advancing clinical ability to treat neuropsychiatric diseases.