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R M Wightman

Publications and source records attributed to R M Wightman.

143 records · Page 8Linked to original sources
PubMed1983

Direct in vivo monitoring of dopamine released from two striatal compartments in the rat.

Microvoltammetric electrodes were used to monitor dopamine released in the caudate nucleus of the rat after electrical stimulation of the medial forebrain bundle. The time resolution of the technique is sufficient to determine in vivo concentration changes on a time scale of seconds. Direct evidence identifying the substance released as dopamine was obtained both voltammetrically and pharmacologically. Administration of alpha-methyl-p-tyrosine terminates the release of dopamine, although tissue stores of dopamine are still present. Thus there appears to be a compartment for dopamine storage that is not available for immediate release. This compartment appears to be mobilized by amfonelic acid, since administration of this agent after alpha-methyl-p-tyrosine returns the concentration of dopamine released by electrical stimulation to 75 percent of the original amount.

Amphetamine↗
PubMed1982

In vivo voltammetry with electrodes that discriminate between dopamine and ascorbate.

Untreated carbon-fiber voltammetric electrodes have been employed as chemical sensors of easily oxidized compounds in the brains of rats anesthetized with chloral hydrate. These electrodes can be used to distinguish dopamine from ascorbate and dihydroxyphenylacetate by the shape of the voltammograms. The electrodes are shown to provide a reproducible response to different neuronal stimuli. The rapid release of dopamine in the caudate nucleus can be measured following a local application of potassium chloride. Intraperitoneal injections of amphetamine also induce an increase of easily oxidized compounds; however, the voltammetry suggests that ascorbic acid, rather than dopamine, is the primary substance detected. Measurements in the cortex or in the caudate nucleus of animals lesioned by prior injection of 6-hydroxydopamine show that a substance with voltammetric properties identical to those of ascorbic acid also increases in concentration in these areas as a result of amphetamine administration.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Determination of gamma-aminobutyric acid by liquid chromatography with electrochemical detection.

gamma-Aminobutyric acid (GABA) has been determined in rat brain by derivatization with 2,4,6-trinitrobenzenesulfonic acid. The derivative and an internal standard, 2,4,6-trinitrophenyl-delta-aminovaleric acid, are extracted into toluene and separated by reversed-phase chromatography. Electrochemical reduction of these derivatives permits picomole measurements of GABA in microgram amounts of brain tissue.

Animals↗
PubMed1982

Use of rapid superfusion to differentiate the release of dopamine from striatal tissue induced by sympathomimetic amines from release induced by potassium.

A rapid superfusion system incorporating a continuous amperometric detector has been employed to study the effects of p-tyramine, d-amphetamine and cocaine on K+-stimulated release of dopamine (DA) from striatal tissue. Qualitative identification of the released substances is made by liquid chromatography with electrochemical detection and DA is established to be the principal substance released following exposure of the tissue to 60 mM K+ in the presence of Ca++. At a superfusion rate of 1 ml/min with a 20 microliter volume tissue holder, d-amphetamine and p-tyramine do not elicit detectable release of endogenous substances. These results are in direct contrast to the significant release of DA observed when striatal tissue is incubated with d-amphetamine for the same time period and suggest that the pools susceptible to release by the sympathomimetic amines are removed by superfusion. When striatal tissue is superfused with a buffer containing 60 mM K+ and cocaine or sympathomimetic amines, the effects of uptake blockade are manifested as an increase in the amount and duration of observed release over that obtained with 60 mM K+. In a competitive study of cocaine and p-tyramine with d-amphetamine, it appears that all three of these agents induce blockade at the same site(s). All of these data are in direct accord with the facilitated exchange diffusion mechanism proposed for the actions of sympathomimetic amines at DA nerve terminals.

Animals↗
PubMed1981

Evaluation of amphetamine-induced in vivo electrochemical response.

A carbon fiber microelectrode is shown to give a potential-dependent dopamine-selective response in rat brain tissue. However, distinct evidence for dopamine release is not obtained with intraperitoneal amphetamine administration (1.8 or 3.7 mg . kg-1). In rats which have been unilaterally depleted of dopamine, the change in electrochemical signal obtained in the lesioned striatum is very similar to that measured on the non-lesioned side following amphetamine administration. This indicates that substances other than dopamine contribute to the observed signals.

Amphetamine↗
PubMed1980

Small-volume electrochemical detector for microcolumn liquid chromatography.

A submicroliter electrochemical detector for liquid chromatography has been designed, using pressure-annealed pyrolytic graphite technology. The analytical performance of this detector was studied in connection with a reversed-phase packed microcapillary column at very low flow-rates. Although the miniaturized version of the electrochemical detector is less sensitive, a direct analysis of a number of urinary metabolites in 0.1--1.0 microliters samples is feasible.

Chromatography, Liquid↗
PubMed1978

In vivo voltammetry: monitoring of dopamine metabolites in CSF following release by electrical stimulation.

An in vivo electrochemical system which continuously records the concentration of metabolites of biogenic amines in small animal CSF is described. A small electrode, immersed in lateral ventricle CSF through a guide cannula, measures the amine metabolites by voltammetric oxidation. The detailed results of HVA release following electrical stimulation of the nigrostriatal pathway in rats are presented and compared with previous perfusion data. All the electrochemical results are verified by independent liquid chromatographic (chemical) analysis.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Competitive oxidation of 6-hydroxydopamine by oxygen and hydrogen peroxide.

Simultaneous oxygen electrode and conventional polarographic measurements show the net concentration of hydrogen peroxide produced by air oxidation of 6-hydroxydopamine is considerably less than that predicted from the known stoichiometry of the reaction. This is due to competitive oxidation of 6-hydroxydopamine by the generated hydrogen peroxide. The presence of ascorbic acid in this reaction also results in significant decreases of hydrogen peroxide under most conditions. The implications of these results to the molecular mechanism of 6-hydroxydopamine neurotoxicity are discussed.

Ascorbic Acid↗
PubMed1976

Intracyclization rates of 6-hydroxydopamine and 6-aminodopamine analogs under physiological conditions.

It is agreed that the neurotoxic action of 6-hydroxydopamine and 6-aminodopamine is related to their ease of oxidation. The initial oxidation products, the p-quinone and p-quinone imine, readily undergo 1,2-intracyclization. These reactions could represent an important loss of active neurotoxic agent available uptake. A variety of substituted 6-aminodopamine analogs was prepared and their formal potentials and cyclization rates were measured accurately. The effect of the balance of ease of oxidation vs. rate of cyclization on their neurotoxicity was examined. The results are in general accord with in vivo lifetimes for 6-hydroxydopamine and 6-aminodopamine in rat caudate nucleus.

Chemical Phenomena↗
PubMedDate not supplied

Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake.

Advances in measurement techniques have enabled the extracellular concentration of dopamine to be monitored inside striatal structures during transient electrical stimulation of the medial forebrain bundle. The observed concentration changes can be accounted for by a mathematical model as a function of the frequency employed and the stimulus duration. Overflow curves can be described by 3 kinetic parameters: the concentration of dopamine released per stimulus pulse, and the Km and Vmax of uptake. In terms of this model, the kinetics of overflow during stimulation is found to be identical in the nucleus accumbens and caudate nucleus with the exception that the Vmax for uptake is lower in the former region. Maximal uptake is also found to be lower in animals with partial lesions of dopamine neurons. Measured concentrations vary with stimulation frequency from 10 to 60 Hz in a manner that can be predicted by the model. Competitive uptake inhibitors have their primary effect on overflow in the limit of low stimulus frequencies. In contrast, D2 antagonists, which increase the concentration of dopamine released per stimulus pulse, have a moderate effect in low and high frequency ranges, but cause a significant maximal increase in extracellular dopamine concentrations at a mid-range frequency. Both calculated response and experimental findings indicate that in the caudate nucleus, the upper frequency for observable uptake inhibition and the characteristic maximum frequency for the receptor-mediated response occur at higher values than in the nucleus accumbens. The model appears to be useful for predicting dopamine extracellular concentrations over a wide range of conditions, and its predictions may be valid when extended to more physiological situations.

Animals↗
PubMedDate not supplied

[The effect of the dopamine neuronal reuptake inhibitor GBR 12909 on the dopaminergic neurotransmission parameters in the rat striatum in vivo].

The aim of the present research was to investigate the effects of the selective dopamine re-uptake inhibitor GBR 12909 (10 mg/kg, i.p.) on dopaminergic neurotransmission in rat striatum. GBR 12909 increased DA levels in microdialysis samples from freely moving rats. In contrast, administration of GBR 12909 slightly decreased the NSD 1015 (50 mg/kg)--induced DOPA accumulation. This result may be explained as a decrease in DA biosynthesis in response to an increasing amount of DA in the synaptic cleft. Fast-scan cyclic voltammetric monitoring of electrically-evoked DA showed significant changes after the drug in DA re-uptake (Km), but not DA release. In conclusion, our results support the notion, that GBR 12909 is a specific DA uptake inhibitor without any transmitter releasing action.

Animals↗