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-DOPA therapy affects the dynamics of fluctuating dopamine concentrations in the striatum on a rapid timescale (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 electrochemical data is largely due to electrode fouling caused by polymerization of L-DOPA and endogenous catecholamines on the electrode surface. Thus, we have systematically optimized 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 cyclic voltammetry. An acute dose of 5 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 ~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 cyclic voltammetry. It provides a methodology that improves the stability and performance of the carbon fiber microelectrode 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 electroanalytical chemistry.

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Fast-scan cyclic voltammetry (FSCV) has proven utility for monitoring rapid neurochemical changes, and for associating these with behavior. Traditional protocols involve collection of 10 voltammograms per second, each comprised of 1000 data points. This was established without consideration for data density, and few studies have evaluated the impact of data collection parameters on data quality. In this work, FSCV data collection protocols were evaluated with an emphasis on reducing sampling rates (number of CVs collected per second) and the number of data points comprising each individual voltammogram. Pairing a 1 Hz sampling rate with voltammograms comprised of 100 data points each reduces the quantity of data by two orders of magnitude (per second) as compared to the traditional protocol. The frequency and duration of transient dopamine fluctuations are dependent on voltammetric sampling rate; however, the information associated with these chemical signals is largely conserved when using this approach. Moreover, collection of data at reduced densities does not significantly impact interpretation of the effects of cocaine on dopamine dynamics when data are normalized to baseline. This research will help guide development of wireless FSCV systems with decreased power requirements, and will facilitate expansion of data collection to many channels operating simultaneously.