Long-Term Monitoring of Brain Dopamine Metabolism In Vivo with Carbon Paste Electrodes

Abstract

This review focuses on the stability of voltammetric signals recorded over periods of months with carbon paste electrodes (CPEs) implanted in the brain. The key interaction underlying this stability is between the pasting oil and brain lipids that are capable of inhibiting the fouling caused by proteins. In brain regions receiving a significant dopaminergic input, a peak due to the methylated metabolites of dopamine, principally homovanillic acid (HVA), is clearly resolved using slow sweep voltammetry. Although a number of factors limit the time resolution for monitoring brain HVA concentration dynamics, the stability of CPEs allows investigations of long-term effects of drugs, as well as behavioral studies, not possible using other in-vivo monitoring techniques.

Development of a voltammetric technique for monitoring brain dopamine metabolism: compensation for interference caused by DOPAC electrogenerated during homovanillic acid detection

“…56,[61][62][63][64][65] In addition, lipids (and other surfactant media) 66,67 can remove surface pasting oil from CPEs, enhancing electron transfer kinetics and improving signal resolution. 64 The voltammetric behaviour of AA at very slow sweep rates at carbon electrodes has been described extensively, 56,63,[68][69][70][71][72][73] as has that of HVA under similar conditions, 29,30,74,75 and the ability of CPE PEA to resolve AA and HVA signals recorded at 10 min intervals in vivo at scan rates as low as 5 mV/s is clear. 29,33,76,77 However, because our aim was to develop a technique to monitor HVA with a time resolution of the order of seconds, the cyclic voltammetric response of AA and HVA at CPE PEA for a scan rate of 1 V/s was determined, initially in separate solutions (Fig.…”

“…5), indicating that both physiological and pharmacological changes in ECF HVA levels could be detected with this significantly improved technique. 29 The linearity of the HVA response, determined using 5-point calibrations (see Fig. 6, inset), was excellent, with R 2 ¼ 0.998.…”

“…Although this lowered the time resolution to one scan every 10 s, it was still vastly superior to literature values of several minutes. 29 Following calibrations with HVA and the interference species, the correction potentials were determined by the iterative method used above for the 1 V/s data. Firstly, I HVA was approximated by I 700 , and plotted versus scan number, giving a graph similar to Fig.…”

“…26,[29][30][31][32][33][34] The advantages and limitations of this approach have been reviewed recently, together with a summary of DA metabolic pathways. 29 The main attraction of the HVA signal recorded with CPEs is its stability over many weeks of monitoring. 35 However, an important drawback with previous IVM studies involving HVA, including those using microdialysis, 36 is the low sampling frequency, which was of the order of 10-30 min intervals.…”

“…Paired tests were used for comparing signals recorded with the same electrode (e.g., before and after a treatment); unpaired tests were used for comparing responses obtained with different electrodes. 29,33,76,77 However, because our aim was to develop a technique to monitor HVA with a time resolution of the order of seconds, the cyclic voltammetric response of AA and HVA at CPE PEA for a scan rate of 1 V/s was determined, initially in separate solutions (Fig. 1).…”