[Frontiers in Bioscience E5, 249-257, January 1, 2013]

Improved techniques for examining rapid dopamine signaling with iontophoresis

Natalie R. Herr1, Robert Mark Wightman1,2

1Department of Chemistry, University of North Carolina at Chapel Hil, Chapel Hill, NC 27599-3290, 2Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290


1. Abstract
2. Introduction
2.1. Tools for studying dopamine neurotransmission in vivo
3. Basic principles of iontophoresis
3.1. Origin of iontophoresis in neurobiology
3.2. Quantification of iontophoretic drug delivery
3.3. Determination of transport numbers
3.4. Effects of retaining currents
3.5. Other factors affecting iontophoretic delivery
4. Iontophoresis in the central nervous system
4.1. Studying the role of dopamine in the striatum with iontophoresis
4.2. Real-time monitoring of iontophoretic delivery
5. Conclusions
6. Acknowledgements
7. References


Dopamine is a neurotransmitter that is utilized in brain circuits associated with reward processing and motor activity. Advances in microelectrode techniques and cyclic voltammetry have enabled its extracellular concentration fluctuations to be examined on a subsecond time scale in the brain of anesthetized and freely moving animals. The microelectrodes can be attached to micropipettes that allow local drug delivery at the site of measurement. Drugs that inhibit dopamine uptake or its autoreceptors can be evaluated while only affecting the brain region directly adjacent to the electrode. The drugs are ejected by iontophoresis in which an electrical current forces the movement of molecules by a combination of electrical migration and electroosmosis. Using electroactive tracer molecules, the amount ejected can be measured with cyclic voltammetry. In this review we will give an introduction to the basic principles of iontophoresis, including a historical account on the development of iontophoresis. It will also include an overview of the use of iontophoresis to study neurotransmission of dopamine in the rat brain. It will close by summarizing the advantages of iontophoresis and how the development of quantitative iontophoresis will facilitate future studies.