Unmasking the Effects of L-DOPA on Rapid Dopamine Signaling with an Improved Approach for Nafion Coating Carbon-Fiber Microelectrodes

L-DOPA has been the gold standard for symptomatic treatment of Parkinson's: disease. However, its efficacy wanes over time as motor complications develop.-Very little is known about how L-DOP.A. therapy affects the dynamics of fluctuating dopamine concentrations in the striatum on a rapid time scale (seconds).. Electrochemical studies investigating the effects of L-DOPA treatment on electrically evoked dopamine release have reported conflicting results with significant variability. We hypothesize that the uncertainty in the electro-chemical data is largely.due to electrode fouling caused by polymerization of L-DOPA and.endogenous catecholarnines on the electrode surface. Thus, we have systematically optiniized-the procedure for fabricating cylindrical, Nafion-coated, carbon-fiber microelectrodes. This has 'enabled. rapid and reliable detection of L-DOPA's effects on. striatal dopamine signaling in intact rat brain-using fast-scan cydic voltammetry. An acute dose of S mg/kg L-DOPA had no significant effect on dopamine dynamics, demonstrating the highly,:efficient regulatory mechanisms at work in -the intact brain. In contrast, administration of 200 mg/kg L-DOPA-significantly increased the amplitude of evoked dopamine 'release by similar to 200%. Overall, this work describes a reliable tool that allows a better measure of L-DOPA augmented dopamine release in vivo, measured using fast-scan eyelid voltammetry. It provides a methodology-that-improves the stability and performance of the carbon-fiber mieroelectrode when studying 'the molecular mechanisms underlying-L-DOPA therapy and also promises to 'benefit a wide variety of studies because-Nafion is so commonly used in electroandrical chemistry.