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Biomedical subjects

J Millar

Publications and source records attributed to J Millar.

At least 109 records · Page 6Linked to original sources

Sub-second striatal dopamine release measured by in vivo voltammetry.

High speed cyclic voltammetry was used to measure electrically stimulated striatal dopamine release in vivo with 25 ms time resolution. Dopamine release after 1 s stimulations was readily detectable and could be manipulated by drugs known to influence dopaminergic neurones. Using data-averaging dopamine release could be detected following stimulus trains as short as 100 ms. The use of carbon fibre microelectrodes gave a spatial resolution better than 5 micron.

Animals↗

Measurement of stimulated dopamine release in the rat by in vivo voltammetry: the influence of stimulus duration on drug responses.

High-speed cyclic voltammetry at carbon fibre microelectrodes was used to monitor stimulated striatal dopamine (DA) release in the anaesthetised rat. The effects of metoclopramide, chlorpromazine, benztropine and dexamphetamine on DA release after 1 s and 10 s stimulations were investigated. The antagonists enhanced DA release most clearly with 1 s stimuli. Benztropine had no effect on DA release with the 10 s stimulations, but elevated release after 1 s trains. Dexamphetamine reduced release with 10 s stimuli but enhanced release after 1 s trains. The results are discussed in terms of neuronal DA uptake and releasable DA pool size.

Animals↗

In vivo voltammetric characterization of low affinity striatal dopamine uptake: drug inhibition profile and relation to dopaminergic innervation density.

Electrical stimulation of the median forebrain bundle evoked dopamine release in the ipsilateral striatum which was monitored with high-speed cyclic voltammetry. After stimulation, the extracellular concentration of dopamine fell due to uptake in a biphasic manner, showing zero-order and first-order components. The zero-order phase corresponded to a Vmax of 42.8 +/- 1.8 nmol/min/g tissue. The uptake system could be blocked by D-amphetamine, methylphenidate and nomifensine, but not by benztropine, amfonelic acid or mazindol. The density of uptake sites showed a correlation with the density of striatal dopamine innervation.

Animals↗

An in vivo voltammetric comparison of the effects of three psychomotor stimulants on electrically evoked neostriatal dopamine release.

The effects of three psychomotor stimulants (mazindol, beta-phenylethylamine and D-phenmetrazine) on electrically evoked neostriatal dopamine release were studied by in vivo voltammetry. Mazindol (10 mg/kg) enhanced release and this effect persisted after dopamine synthesis inhibition by alpha-methyl-p-tyrosine. beta-Phenylethylamine (100 mg/kg) caused a large decrease in stimulated dopamine release and exerted no effect after dopamine synthesis inhibition. D-Phenmetrazine (45 mg/kg) enhanced dopamine release on the first post-drug stimulation and also restored release after dopamine synthesis inhibition. Disruption of vesicular dopamine storage by Ro 4-1284 abolished electrically stimulated dopamine release. Only D-phenmetrazine was able to cause dopamine release following Ro 4-1284. These results imply different biochemical modes of action of these three stimulants.

Amphetamine↗

Ascorbic acid does not modulate stimulated dopamine release: in vivo voltammetric data in the rat.

Electrical stimulation of the nigrostriatal pathway released dopamine (DA) in the striatum of the anaesthetized rat. The level of DA released by 10-s stimulus trains was measured by high-speed cyclic voltammetry. Metoclopramide (10 mg/kg) increased DA release by approximately 20%. Apomorphine (1.76 mg/kg) caused a approximately 40% decrease in release which was blocked by metoclopramide. Ascorbate (1.76 g/kg) had no effect on stimulated DA release. Furthermore, pretreatment of rats with ascorbate trebled the striatal extracellular ascorbate level, but failed to modify the effects of metoclopramide and apomorphine on DA release. We conclude that ascorbate has no effect on the presynaptic autoreceptors that modulate striatal DA release in vivo.

Animals↗

Electrochemical, pharmacological and electrophysiological evidence of rapid dopamine release and removal in the rat caudate nucleus following electrical stimulation of the median forebrain bundle.

Fast cyclic voltammetry was used to monitor the release of electroactive material in the striatum following electrical stimulation of the median forebrain bundle. The released material was shown to be dopamine by electrochemical, pharmacological and neurophysiological means. The material gave a voltammogram identical to that of iontophoretically applied dopamine but not DOPAC. Release was increased by L-DOPA, the metabolic precursor of dopamine. NSD 1015, an inhibitor of dopa decarboxylase, and alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor decreased release. Reserpine, which disrupts vesicular dopamine storage, abolished release. Parachlorophenylalanine, a tryptophan hydroxylase inhibitor, had no effect. Finally, square wave stimulation was only effective when pulses longer than 0.5 ms were used. This indicated stimulation of very fine unmyelinated fibres, consistent with the known morphology of nigrostriatal dopamine fibres.

Animals↗

A randomised trial of cyclophosphamide pretreatment ('priming') before short-duration chemotherapy for small cell lung carcinoma.

Forty-five patients with small cell anaplastic carcinoma of the bronchus were treated with four four-weekly courses of a combination of cyclophosphamide, vincristine and methotrexate. Randomisation was carried out to determine whether they received in addition 1 g/m2 of cyclophosphamide 1 week before the three-drug therapy. Patients with limited disease received radiotherapy after their chemotherapy. Myelosuppression was similar in the two groups, but the additional cyclophosphamide did not improve remission duration or survival. Confining the chemotherapy to four courses did not give shorter survival times to those reported in other studies.

Adult↗

Striatal dopamine uptake in the rat: in vivo analysis by fast cyclic voltammetry.

Electrical stimulation of the median forebrain bundle of the chloral hydrate anaesthetised rat evoked dopamine release in the ipsilateral striatum, which was monitored with fast cyclic voltammetry. On cessation of stimulation, the extracellular concentration of dopamine fell to sub-detectable levels over a period of about 15 s. This fall appeared to be due to a saturable, low affinity uptake system that could be inhibited by nomifensine (20 mg/kg i.p.). These experiments constitute the first characterisation of a dopamine uptake mechanism obtained in the intact animal.

Animals↗

Antagonism of 5-hydroxytryptamine-evoked excitation in the superficial dorsal horn of the cat spinal cord by methysergide.

Ionophoretically applied methysergide was tested on 9 units excited by 5-hydroxytryptamine (5-HT) recorded in the superficial dorsal horn of cat spinal cord. In all cases, methysergide produced a prolonged and repeatable antagonism of the excitatory action of 5-HT, but it had no effect on glutamate-evoked activity or on that caused by adequate stimulation of the receptive field. This result supports the proposal that excitation by 5-HT is a direct synaptic effect, and not a 'non-specific' action.

Animals↗

Regional differences in extracellular ascorbic acid levels in the rat brain determined by high speed cyclic voltammetry.

High speed cyclic voltammetry was used in combination with pressure ejection of ascorbate oxidase for the determination of extracellular ascorbic acid within the brain of the anaesthetized rat. Large variations in absolute levels of ascorbate were found between animals although distribution patterns showed a good degree of reproducibility. Ascorbate levels in the white matter of the corpus callosum were found to be higher than in adjacent areas of grey matter (striatum and cortex).

Animals↗

A double-cycle high-speed voltammetric technique allowing direct measurement of irreversibly oxidised species: characterisation and application to the temporal measurement of ascorbate in the rat central nervous system.

The oxidation of ascorbic acid at carbon fibre microelectrodes is irreversible due to rapid hydration of the product. This feature has been employed in the development of a voltammetric assay using a double-cycle voltage sweep. The difference between the current generated on the first and second anodic sweeps is proportional to the concentration of ascorbate. The characterisation and application of the method are discussed.

Animals↗

Receptive fields and responses to ionophoretically applied noradrenaline and 5-hydroxytryptamine of units recorded in laminae I-III of cat dorsal horn.

Recordings were made with carbon fibre microelectrodes from 87 units in laminae I, II and III of the spinal cord in anaesthetized cats, and responses of the units to ionophoretically applied noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were observed. Units with low threshold receptive fields were situated in laminae II and III, while those with high threshold or wide dynamic range fields were mainly restricted to laminae I and II. NA excited nearly half of the units in laminae I and II but had no effect on most units in lamina III. 5-HT excited 68% of the units and these were distributed throughout all 3 laminae. Excitations, particularly by 5-HT, could be very prolonged. NA and 5-HT excited units in all 3 receptive field classes. A few units in lamina I were inhibited. It is suggested that the cells recorded from in the present experiments may be inhibitory interneurones which act on large dorsal horn cells or on their primary afferent inputs.

Animals↗

Accuracy and value of the Hemoccult test in symptomatic patients.

Hemoccult faecal occult blood testing is widely advocated as a screening test for colorectal cancer but few studies have shown its correlation with conventional methods of investigation for colorectal disease. In a prospective study of 802 symptomatic patients with suspected colorectal disease there was good patient compliance (92.5%) and a high specificity for colorectal cancer (85.4%). The false positive rate was 8.6% (12 of 140 patients with positive results), and while the test result was positive in 22 of 26 colonic cancers the false negative rate for rectal cancer (45.4%) should not detract from its value as a screening test if proper digital anorectal and proctosigmoidoscopic examination are widely practised. A positive Hemoccult test result is a useful indicator for the need to proceed to full colorectal investigation, including colonoscopy.

Adolescent↗

A simple noise clipping circuit for neurophysiological audio monitors.

A very simple circuit is described which removes the low amplitude components of audio frequency signals, leaving the positive and negative peaks superimposed on a flat baseline. The clipping is symmetrical and adjustable in gain. Thus the baseline noise in audio monitors used in extracellular single-unit recording can be attenuated. This enhances the aural discrimination of single units and reduces aural fatigue.

Auditory Perception↗

Dendrite spikes recorded extracellularly from dorsal horn neurones.

(1) Extracellular action potentials were recorded from laminae IV--VI dorsal horn cells, using multibarrel carbon fibre micro electrodes. The amplitude and shape of the extracellular spike, the receptive field, and the response to iontophoretic glutamate ion, were investigated for each cell. (2) Of the 172 units isolated, 48 (28%) could be recorded from over a range of microelectrode tip depths greater than 100 micrometers. The sensitivity of these 'trackable' cells to glutamate was investigated at different depths; 13/48 (27%) had zones where they were insensitive to glutamate. (3) From the data on spike shapes and glutamate sensitivity, it is argued that dendritic spikes can occur in these cells.

Action Potentials↗