Application of intracerebral dialysis and in vivo voltammetry to pharmacological and physiological studies of amine neurotransmitters.
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3,4-Dihydroxyphenylacetic Acid↗
Biomedical subjects
N T Maidment
Publications and source records attributed to N T Maidment.
In vivo voltammetric and behavioural evidence for somatodendritic autoreceptor control of mesolimbic dopamine neurones.
Somatodendritic autoreceptor control of mesolimbic dopamine neurones was assessed using in vivo differential pulse voltammetry to monitor dopamine metabolism in the nucleus accumbens following infusion of haloperidol or dopamine into the ipsilateral ventral tegmental area (VTA) of chloral hydrate anaesthetized rats. Haloperidol (2.5 micrograms/0.5 microliters) produced an increase in dihydroxyphenylacetic acid (DOPAC) levels (45%) whilst dopamine produced a transient decrease (38%). In three experiments this decrease was smaller and was followed by a large increase in DOPAC levels (108-208%). However, the results of radiolabelled drug diffusion studies suggested that the secondary rise in DOPAC in the nucleus accumbens may be due to diffusion of dopamine following infusion into the VTA. In a separate set of experiments rats were injected with haloperidol (2.5 micrograms/0.5 microliters) bilaterally into the VTA and their behaviour monitored using doppler shift radar. Haloperidol infusion produced a phase of increased exploratory behaviour lasting approximately 30 min. Both sets of data support previous electrophysiological studies suggesting the presence of functional dopamine somatodendritic autoreceptors in the mesolimbic system. The results further demonstrate the applicability of in vivo voltammetry for study of the effects of drugs on discrete receptor populations.
Animals↗
Differential pulse voltammetry: simultaneous in vivo measurement of ascorbic acid, catechols and 5-hydroxyindoles in the rat striatum.
This paper describes carbon fibre electrodes that can simultaneously monitor changes in ascorbic acid, dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in vivo in the rat striatum using differential pulse voltammetry. The separation between DOPAC and 5HIAA oxidation is improved and the size of the 5HIAA peak decreased by the removal of uric acid using the enzyme uricase indicating that uric acid oxidation may contribute to the oxidation peak at + 300 mV. Haloperidol (0.5 mg/kg) decreased ascorbic acid and 5HIAA but increased DOPAC and HVA while D-amphetamine (3 mg/kg) increased ascorbic acid, decreased DOPAC and HVA but had no effect on 5HIAA. These electrodes should be a useful means of investigating interactions between dopamine and serotoninergic systems in vivo.
3,4-Dihydroxyphenylacetic Acid↗
Changes in monoamine metabolites measured by simultaneous in vivo differential pulse voltammetry and intracerebral dialysis.
A direct comparison has been made of the drug-induced changes in extracellular levels of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid measured using intracerebral dialysis and differential pulse voltammetry with carbon fibre electrodes. The comparison was carried out in chloral hydrate anaesthetized rats with a pretreated carbon fibre electrode implanted in one striatum and an intracerebral dialysis loop in the contralateral striatum. 3,4-Dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the dialysis perfusates were assayed by high pressure liquid chromatography with electrochemical detection. d-Amphetamine (2 mg/kg) decreased extracellular 3,4-dihydroxyphenylacetic acid and the height of the 3,4-dihydroxyphenylacetic acid oxidation peak, while haloperidol (0.5 mg/kg) increased 3,4-dihydroxyphenylacetic acid levels measured in the perfusates and the height of the 3,4-dihydroxyphenylacetic acid oxidation peak. In these experiments there were parallel changes in 3,4-dihydroxyphenylacetic acid levels and peak height and a close correlation between these changes. Tranylcypromine (10 mg/kg) produced an almost parallel decrease in extracellular 5-hydroxyindoleacetic acid (dialysis) and the height of the 5-hydroxyindoleacetic acid oxidation peak, with similar percentage changes and good correlation values being obtained. However, while 5-hydroxy-L-tryptophan (25 mg/kg) increased both the 5-hydroxyindoleacetic acid levels and the height of the 5-hydroxyindoleacetic acid oxidation peak, 5-hydroxyindoleacetic acid in the dialysis perfusates showed a greater increase than the oxidation peak. The results show a close correlation between changes in extracellular 3,4-dihydroxyphenylacetic acid and its respective voltammetric peak and strongly support the use of in vivo differential pulse voltammetry for monitoring dopamine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dihydroxyphenylacetic Acid↗
Acute administration of clozapine, thioridazine and metoclopramide increases extracellular DOPAC and decreases extracellular 5-HIAA, measured in the nucleus accumbens and striatum of the rat using in vivo voltammetry.
Changes in the extracellular levels of dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-indoleacetic acid (5-HIAA) after acute administration of clozapine (50 mg/kg s.c.), thioridazine (20 mg/kg s.c.) and metoclopramide (5 mg/kg s.c.), were monitored using in vivo voltammetry with micro-carbon electrodes implanted in the nucleus accumbens and striatum of the rat anaesthetised with halothane/N2O. Both clozapine and thioridazine increased extracellular levels of DOPAC in the striatum and the nucleus accumbens. The maximum increases with clozapine were 60% and 86% in the nucleus accumbens and striatum and 44% and 55% with thioridazine. Both neuroleptics also decreased the extracellular level of 5-HIAA in these regions of the brain. Metoclopramide increased the extracellular level of DOPAC in the nucleus accumbens (42%) and the striatum (57%) and significantly decreased the level of 5-HIAA in the nucleus accumbens. These results suggest that the two so-called atypical neuroleptics, clozapine and thioridazine, do not have selective effects on the metabolism of dopamine in vivo in the nucleus accumbens after acute administration. Furthermore, neuroleptic-induced increases in dopamine metabolism are accompanied by reciprocal decreases in 5-hydroxytryptamine metabolism in vivo.
3,4-Dihydroxyphenylacetic Acid↗
Post-mortem dopamine dynamics assessed by voltammetry and microdialysis.
The effects of total brain ischemia (decapitation) on striatal extracellular levels of dopamine (DA) dihydroxyphenyl acetic acid (DOPAC) and ascorbic acid (AA) in chloral hydrate anesthetized rats were monitored at 1-min intervals by differential normal pulse voltammetry (DNPV) with numerical deconvolution of the catechol peak. Changes in pH were assessed by the shift of AA oxidation potential and incorporated into the computational procedure. The AA peak showed a sharp, short-lived (less than 15 min) postdecapitation rise, followed by a slower secondary increase. The DA signal increased 100-fold in the first 20 min followed by a slow decline. DOPAC levels fell 80% within 15 min after death. The post-mortem changes in extracellular DA and DOPAC were verified by a similar experiment using microdialysis. These observations probably reflect massive release and impaired uptake of DA combined with reduced monoamine oxidase activity. Changes in membrane permeability to DOPAC as a consequence of a post-mortem drop in pH may also contribute to the decline in extracellular DOPAC levels.
3,4-Dihydroxyphenylacetic Acid↗