Probing Presynaptic Regulation of Extracellular Dopamine with Iontophoresis

Abstract

Iontophoresis allows for localized drug ejections directly into brain regions of interest driven by the application of current. Our lab has previously adapted a method to quantitatively monitor iontophoretic ejections. Here those principles have been applied in vivo to modulate electrically evoked release of dopamine in anesthetized rats. A neutral, electroactive marker molecule that is ejected purely by electroosmotic flow (EOF) was used to monitor indirectly the ejection of electroinactive dopaminergic drugs (raclopride, quinpirole, and nomifensine). Electrode placements were marked with an iontophoretically ejected dye, pontamine sky blue. We show that EOF marker molecules, acetaminophen (AP) and 2-(4-nitrophenoxy) ethanol, have no effect on electrically evoked dopamine release in the striatum or the sensitivity of electrode. Additionally, we establish that a short, 30 second ejection of raclopride, quinpirole, or nomifensine with iontophoresis is sufficient to affect autoreceptor regulation and the re-uptake of dopamine. These effects vary in lifetime, indicating that this technique can be used to study receptor kinetics.