title: Unmasking the Effects of L-DOPA on Rapid Dopamine Signaling with an Improved Approach for Nafion Coating Carbon-Fiber Microelectrodes.
abstract: 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 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 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.
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Lingjiao
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Elina
authors.initials: E
authors.lastname: Thomas
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: White
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Smith
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Christie A
authors.initials: CA
authors.lastname: Lee
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Wilson
authors.affiliation: Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Sombers
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002244:Carbon / Q000737:chemistry*; D000077482:Carbon Fiber; D004298:Dopamine / Q000032:analysis*; D055664:Electrochemical Techniques; D004567:Electrodes, Implanted; D005071:Evoked Potentials / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008839:Microelectrodes; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000077482:Carbon Fiber; D007980:Levodopa; D002244:Carbon; D004298:Dopamine