Homogeneous mechanism of ascorbic acid interference in hydrogen peroxide detection at enzyme-modified electrodes.
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Ascorbic Acid↗
Biomedical subjects
R D O'Neill
Publications and source records attributed to R D O'Neill.
Anomalously high concentrations of brain extracellular uric acid detected with chronically implanted probes: implications for in vivo sampling techniques.
The height of peak 2, h2, recorded using linear sweep voltammetry with 350-micron-diameter carbon paste electrodes in rat striatum was measured from the day of implantation (day 0) to 4 months after surgery. The value of h2 was at a minimum on day 0 (0.6 +/- 0.2 nA; n = 20), rose sharply to a maximum on day 2 (6.3 +/- 0.9 nA; n = 12), and decreased to a stable level by day 7 (3.3 +/- 0.7 nA; n = 16), which lasted for 4 months (3.2 +/- 0.6 nA; n = 9). These changes were shown by microinfusion of uricase to be due to variations in the concentrations of extracellular uric acid, although h2 appears to have a small baseline contribution of approximately 0.3 nA from 5-hydroxyindoleacetic acid. The stable value of h2 recorded under chronic conditions was estimated to correspond to a minimal uric acid concentration of 50 mumol/L, which represents a 10-fold increase in the extracellular level of this purine metabolite compared with the initial (acute) value. Very similar results were obtained using a microdialysis technique that detected uric acid directly. These estimates of striatal uric acid concentration are in marked contrast to those obtained using 40-micron diameter carbon fiber electrodes, which showed a decrease from the acute preparation to less than 1 mumol/L under chronic conditions. Large values of h2 were also recorded with chronically implanted paste electrodes in the hippocampus and frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Stearate-modified carbon paste electrodes for detecting dopamine in vivo: decrease in selectivity caused by lipids and other surface-active agents.
Electrochemical characteristics of dopamine, ascorbic acid, and ferrocyanide measured with carbon-Nujol paste electrodes (CPEs) and stearate-modified carbon paste electrodes (SMEs) before and after treatment with either surfactant (Triton-X), lipid (phosphatidylethanolamine), or brain tissue indicate that the lipophilic nature of the brain destroys the selectivity of SMEs for dopamine by removing the hydrophobic elements from the electrode surface. Measurements of the degree and time-course of changes in surface capacitance of SMEs following contact with surface-active agents support this conclusion. The results suggest that SMEs cannot be used to detect dopamine unambiguously in vivo and emphasize the need to characterize electrochemical sensors in an environment similar to that of intended applications.
Carbon↗
Uric acid levels and dopamine transmission in rat striatum: diurnal changes and effects of drugs.
Carbon paste disc electrodes were used to detect voltammetrically changes in the extracellular concentration of the purine metabolite, uric acid, and the dopamine metabolite, homovanillic acid (HVA), in the striatum of unanaesthetized, unrestrained rats under a variety of conditions. The motor activity level for each rat was recorded between the electrochemical scans. In totally unperturbed animals, there was a significant correlation between the levels of the two metabolites during the bright, relatively inactive, period of the diurnal cycle. During much of the dark (active) phase of the cycle, however, the uric acid signal showed no significant change compared with the light-on period, in contrast to the HVA signal which showed a marked increase. Significant variations in the concentration of striatal uric acid were observed during the switch-over from light to dark and dark to light conditions. The unilateral infusion of gamma-aminobutyric acid, taurine and haloperidol into the substantia nigra caused increases in the height of both the uric acid and HVA peak in the ipsilateral striatum; the size of these changes showed a significant correlation. Variable changes occurred on the contralateral side where no correlation was observed. Intraperitoneal administration of the mixed dopamine-receptor agonist, apomorphine, and the mixed antagonist, haloperidol, did not affect striatal uric acid levels significantly. These results suggest that, although there are conditions where parallel changes in dopamine release/receptor-activation and uric acid levels do occur in the striatum, neither the release of dopamine nor activation of dopamine receptors need necessarily lead to changes in the extracellular concentration of uric acid.
Animals↗
The effects of anxiolytic and anxiogenic benzodiazepine receptor ligands on motor activity and levels of ascorbic acid in the nucleus accumbens and striatum of the rat.
The effects of the anxiolytic benzodiazepine flurazepam and the anxiogenic beta-carboline N-methyl-beta-carboline-3-carboxylate (FG 7142) were measured in unanaesthetised rats. Changes in motor activity, using a Doppler-shift microwave device, and in the extracellular concentration of ascorbate in the striatum and nucleus accumbens, using linear sweep voltammetry with carbon paste electrodes, were monitored continuously over a period of 7 days. Both motor activity and release of ascorbate were greater during the dark than the light period; regression analysis showed a high correlation coefficient for motor activity vs release of ascorbate. The two drugs caused similar changes in this diurnal pattern. A single intraperitoneal injection of either flurazepam or FG 7142 at the end of the light period was followed by a reduction in the nocturnal rise of motor activity and of levels of ascorbate in both the nucleus accumbens and striatum. However, whereas the correlation coefficient for motor activity vs the level of ascorbate in both the nucleus accumbens and striatum remained high after the injection of flurazepam, there was a breakdown of the correlation on the day after the injection of FG 7142, followed by recovery.
Animals↗
Dopamine in the basal ganglia and benzodiazepine-induced sedation.
The effects of the anxiolytic benzodiazepine flurazepam on motor activity and the turnover of dopamine were measured in rats. Changes in motor activity were measured using a doppler-shift device; changes in extracellular homovanillic acid (HVA), monitored by linear sweep voltammetry with carbon paste electrodes implanted in the striatum and nucleus accumbens and ex vivo measurements of changes in 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in the striatum and nucleus accumbens were used as indices of changes in the turnover of dopamine. Injection of vehicle increased the nocturnal rise in the concentration of HVA and the ex vivo DOPAC/DA ratio in the nucleus accumbens. Injection of flurazepam decreased the nocturnal rise in HVA and DOPAC/DA ratio in the nucleus accumbens below control levels. There was also a decrease in the nocturnal rise in motor activity. Neither injection of vehicle nor injection of flurazepam caused changes in either the concentration of HVA or the DOPAC/DA ratio in the striatum. The correlation coefficient for motor activity compared to concentration of HVA remained high for the nucleus accumbens but was reduced for the striatum after administration of flurazepam. The results suggest that the sedative effect of flurazepam may be due to an action on the mesolimbic but not the nigrostriatal dopaminergic pathway.
3,4-Dihydroxyphenylacetic Acid↗
In vivo voltammetry--present electrodes and methods.
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Animals↗
Effects of an anxiogenic benzodiazepine receptor ligand on motor activity and dopamine release in nucleus accumbens and striatum in the rat.
The effects of the anxiogenic beta-carboline FG 7142 (N-methyl-beta-carboline-3-carboxylate) on motor activity and dopamine release in nucleus accumbens and striatum were measured in the rat. Changes in extracellular homovanillic acid (HVA) concentration, monitored by computer-controlled linear sweep voltammetry with carbon-paste electrodes, were used as an index of changes in dopamine release. An intraperitoneal injection of FG 7142 was followed by an inhibition of the nocturnal rise in motor activity and in dopamine release in nucleus accumbens, but not striatum. Two days after the drug injection, dopamine release in nucleus accumbens returned to control level and then increased on days 3-6 after the injection; there was no delayed change in motor activity or in striatal dopamine release. In parallel experiments using ex vivo changes in the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC) to dopamine as an index of changes in dopamine turnover, a similar early depression and delayed increase of dopamine turnover in nucleus accumbens, with no change in striatum, was found after an intraperitoneal injection of FG 7142. Regression analysis of motor activity versus dopamine release showed a decrease in correlation between these 2 parameters for nucleus accumbens but not striatum after FG 7142 injection. These results suggest that the inverse benzodiazepine receptor agonist FG 7142 has a biphasic effect on dopamine release from mesolimbic neurons and support the hypothesis that dopamine release in nucleus accumbens and striatum has a modulatory effect on the control of motor activity but does not play a determining role in the regulation of movement.
3,4-Dihydroxyphenylacetic Acid↗
Effects of intranigral injection of taurine and GABA on striatal dopamine release monitored voltammetrically in the unanaesthetized rat.
Linear sweep voltammetry with carbon-paste electrodes was used to detect changes in the extracellular concentration of homovanillic acid (HVA) in the striatum of unanaesthetized rats; under the present experimental conditions, changes in the HVA signal were used as an index of striatal dopamine release. The effects of unilateral intranigral infusion of saline, sucrose, taurine, GABA and the putative taurine-receptor antagonist, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide (TAG), on the HVA signal were monitored in the striatum on the two sides of the brain. Both taurine and GABA caused an increase in the extracellular concentration of HVA which was significantly greater in the striatum on the side of the injection compared with the contralateral side. The effect of TAG varied between animals. The results are discussed in terms of the role of taurine as a possible neuromodulator in the substantia nigra and in the light of the suggestion that different pathways are involved in taurine- and GABA-induced contraversive circling.
Animals↗
Adenosine modulation of striatal neurotransmitter release monitored in vivo using voltammetry.
Linear sweep voltammetry with carbon-paste electrodes was used to record simultaneously changes in the extracellular concentration of ascorbic acid, uric acid and homovanillic acid (HVA) in the striatum of unanaesthetized rats. The ascorbate signal was used as an index of excitatory amino acid release, whereas the HVA signal reflects changes in dopamine release. Microinjection of 2-chloroadenosine depressed both the ascorbate and the HVA signals; the infusion of adenosine deaminase increased the amplitude of the two signals. These results, considered in the light of lesion + binding studies, suggest that released endogenous adenosine may modulate the release of transmitter from both corticostriatal and nigrostriatal terminals. The effect of adenosine deaminase on the urate signal provides preliminary evidence that changes in this signal may reflect variations in the release of adenosine.
Adenosine↗
Microcomputer-controlled voltammetry in the analysis of transmitter release in rat brain.
Microcomputer-based linear sweep voltammetry with carbon-paste electrodes has the following features: Subtraction of the background current produces a voltammogram with three well-resolved peaks: an ascorbate signal reflecting excitatory amino acid release; a uric acid signal that may be related to purine metabolism; and an HVA signal that is an index of dopamine release under certain conditions. Voltammograms from up to eight electrodes (for example, four electrodes in two rats or two electrodes in four rats) can be recorded simultaneously together with motor activity for each rat over extended periods. Electrodes remain stable over periods of many weeks as measured by the constancy of the mean peak height in a 24-hr period. Microcomputers in voltammetry provide flexibility of all recording parameters and a wide variety of methods of analysis. The combination of stable electrodes and the ability to monitor over extended periods means that interactions between transmitters in different brain regions and their relation to physiological processes can be studied.
Amino Acids↗
Effects of light reversal on the circadian pattern of motor activity and voltammetric signals recorded in rat forebrain.
To investigate the functional relationships between the circadian changes in rat motor activity and changes in the extracellular concentration of ascorbic acid and homovanillic acid (HVA) monitored in the striatum and nucleus accumbens, reversal of the light/dark cycle was used to disturb the pattern of motor activity. Microcomputer-controlled linear sweep voltammetry with carbon-paste electrodes was used to continuously monitor circadian changes in the ascorbate signal and the HVA signal simultaneously in nucleus accumbens and striatum over a 13 day period in unrestrained rats; total motor activity for each animal was also recorded. Regression analyses were carried out on each day's data to investigate the relationships between motor activity and the two voltammetric signals. During days 1-5, the lighting was on normal 12/12 light/dark cycle and high correlations were observed. Reversal of the light/dark cycle on day 6 caused an immediate change in the pattern of motor activity and electrochemical signals; by days 7-8 after light reversal the relationships between lighting, ascorbate, HVA and motor activity were reestablished under the new lighting conditions. During the intervening period, however, there was a complete breakdown in some of the correlations. The findings are discussed in the light of the hypothesis that changes in brain extracellular ascorbate reflect changes in the release of excitatory amino acids, and in terms of a recent model of the role, in the control of motor activity, for cortical and mesencephalic inputs to forebrain subcortical regions.
Animals↗
Circadian changes in extracellular ascorbate in rat cortex, accumbens, striatum and hippocampus: correlations with motor activity.
We have used linear sweep voltammetry with carbon-paste electrodes to monitor changes in the ascorbate signal simultaneously in rat frontal cortex, nucleus accumbens, striatum and hippocampus together with motor activity. The relative amplitude of the ascorbate signal recorded in the four regions corresponded to the relative density of excitatory amino acid (EAA) transmission determined by other methods; this result provides further evidence that the ascorbate signal may be used as an index of EAA release. Changes in motor activity were associated with changes in the ascorbate signal; linear regression analysis for motor activity versus the ascorbate signal revealed differences between the release of ascorbate in the four brain regions.
Animals↗
Simultaneous monitoring of dopamine release in rat frontal cortex, nucleus accumbens and striatum: effect of drugs, circadian changes and correlations with motor activity.
Changes in homovanillic acid concentration, recorded in vivo by voltammetry with carbon-paste electrodes, were used as an index of dopamine release. With electrodes implanted in frontal cortex, nucleus accumbens and striatum, the pattern of dopamine release was monitored simultaneously in the three brain regions together with the rats' motor activity. Changes in response to the systemic administration of dopamine-receptor agonists and antagonists were used as an index of feedback control of dopamine release. The relationships between dopamine release and motor activity, as well as that between dopamine release in the different brain regions, were investigated by calculating correlation coefficients for data collected over 24-h periods. The results show that dopamine release in frontal cortex is subject to little feedback regulation, that there is no nocturnal increase and no correlation with motor activity. Dopamine release in accumbens and striatum follows a very different pattern. There was a high correlation between dopamine release in these two regions on both sides of the brain; the correlation between the accumbens and the ipsilateral striatum was the highest. Dopamine release in both regions shows evidence of considerable feedback regulation, a nocturnal increase and a high correlation with motor activity. The importance of the accumbens in relation to the level of motor activity is supported by the finding that the correlation coefficient between motor activity and dopamine release in this structure was significantly higher than that between activity and release in the striatum.
Animals↗
Detection of homovanillic acid in vivo using microcomputer-controlled voltammetry: simultaneous monitoring of rat motor activity and striatal dopamine release.
Linear sweep voltammograms recorded with carbon paste electrodes in the striatum of the unanaesthetised, unrestrained rat show three separate peaks. The effect on peak 3 of either unilateral 6-hydroxydopamine lesion of the substantia nigra or intraperitoneal administration of alpha-methyl-paratyrosine, supports our earlier conclusion that peak 3 is due to the dopamine metabolite homovanillic acid. Administration of gamma-butyrolactone, which inhibits firing of dopaminergic nigrostriatal neurones, produces an immediate decrease in striatal homovanillic acid, followed by a prolonged increase. Dopamine-receptor agonists and antagonists produce changes in the extracellular concentration of homovanillic acid which are predicted by their effects on dopamine release. Simultaneous monitoring of total motor activity and homovanillic acid show significant correlation between these two parameters. The usefulness of this technique for monitoring dopamine release is critically evaluated in the light of these results.
4-Butyrolactone↗