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Biomedical subjects

M Fillenz

Publications and source records attributed to M Fillenz.

At least 55 records · Page 3Linked to original sources
PubMed1990

Tail pinch-induced changes in the turnover and release of dopamine and 5-hydroxytryptamine in different brain regions of the rat.

Tail pinch was administered through a paper clip attached to the rat's tail. The ex vivo changes in the metabolite/transmitter ratio were used as a measure of changes in the turnover of dopamine and 5-hydroxytryptamine. After a 2-min tail pinch dopamine turnover was increased in the striatum but not in the frontal cortex, hypothalamus or olfactory tubercle; 5-hydroxytryptamine turnover was increased in frontal cortex and hippocampus and was unchanged in striatum, hypothalamus and olfactory tubercle. Microdialysis was used to monitor the changes in extracellular neurotransmitter and metabolite concentrations during and after tail pinch. A 5-min tail pinch caused a rapid rise of both dopamine in the striatum and 5-hydroxytryptamine in the hippocampus. There was a smaller increase in the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid and only a non-significant increase in the dopamine metabolite 3,4-dihydroxyphenylacetic acid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

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↗
PubMed1989

Both systemic and local administration of benzodiazepine agonists inhibit the in vivo release of 5-HT from ventral hippocampus.

The effects of benzodiazepine- and GABAA-receptor agonists and antagonists on the release and metabolism of 5-HT were measured in the ventral hippocampus of freely moving rats using microdialysis. Systemic injections of the benzodiazepine agonists, flurazepam and diazepam reduced the levels of 5-HT while the partial inverse agonist, FG 7142 (N-methyl-beta-carboline-3-carboxamide), had no effect. Local perfusion of flurazepam through the dialysis probe also decreased the release of 5-HT in the ventral hippocampus, an effect which was completely blocked by the benzodiazepine antagonist, Ro15-1788 (flumazenil). Local application of the GABAA agonist muscimol had no effect on the release of 5-HT, while the antagonist picrotoxin, administered locally, caused a 4-fold enhancement of release of 5-HT. Picrotoxin also resulted in a complete block of the inhibitory effect of flurazepam on release of 5-HT. None of these drugs caused significant changes in the levels of the metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in the ventral hippocampus. These results suggest that the inhibitory effect of flurazepam on the release of 5-HT is mediated by benzodiazepine/GABAA receptors in the hippocampus and that GABA exerts a tonic inhibitory effect on the release of 5-HT in the region of the brain.

Animals↗
PubMed1989

Rapid changes in striatal ascorbate in response to tail-pinch monitored by constant potential voltammetry.

The first peak in the voltammogram recorded with linear sweep and a carbon paste electrode implanted in the rat striatum is due to the oxidation of ascorbic acid. When the potential is held at a level slightly positive to this peak a current is recorded which is abolished by the microinjection of ascorbic acid oxidase in the vicinity of the electrode; this suggests that it is due to the oxidation of ascorbate. This current shows the same diurnal variation as the size of the ascorbate peak and its rise and fall coincides with the onset and offset of motor activity. A tail-pinch applied through a paper clip causes an immediate rise in the ascorbate current which begins to fall as soon as the paper clip is removed. Measurement of the ascorbate current at constant potential provides a technique for monitoring rapid changes in extracellular brain ascorbate in response to physiological stimuli.

Animals↗
PubMed1988

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↗
PubMed1988

K+-dependent stimulation of dopamine synthesis in striatal synaptosomes is mediated by protein kinase C.

Dopamine synthesis rate was measured in striatal synaptosomes. Removal of Na+ increased synthesis rate; this was blocked in Ca2+-free medium and by addition of the Ca2+/calmodulin inhibitor N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide (W7). The increase in dopamine synthesis rate caused by the addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was blocked by the protein kinase C inhibitor polymyxin B. K+-stimulated synthesis was unchanged in Ca2+-free medium or by addition of W7; it was blocked by polymyxin B. The effect of 50 mM K+ was additive with that of 8-Br cyclic AMP and of Na+ removal; the combined effect of 50 mM K+ and TPA was no greater than that of either alone. These results suggest that stimulation of dopamine synthesis in striatal synaptosomes by 50 mM K+ is mediated by protein kinase C.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Protein kinase C mediates the stimulation by somatostatin of dopamine synthesis in the rat striatum and nucleus accumbens.

In experiments using a synaptosomal preparation from the striatum and nucleus accumbens, somatostatin caused a dose-dependent increase in dopamine synthesis. This increase was additive with that produced by 8-BrcAMP but not with that produced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and was blocked by the protein kinase C inhibitor polymyxin B (PMB). These findings suggest that stimulation of dopamine synthesis by somatostatin is mediated by activation of protein kinase C.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Cholecystokinin stimulates dopamine synthesis in synaptosomes by a cyclic AMP-dependent mechanism.

The effects of different fragments of cholecystokinin (CCK) on dopamine synthesis were studied in synaptosomal preparations from the striatum, substantia nigra, and frontal cortex. In striatal synaptosomes, dopamine synthesis rate measured by dopamine accumulation was 12.5% lower than that measured by 3,4-dihydroxyphenylalanine (DOPA) accumulation; however, K+-accelerated synthesis was the same for both methods. Synthesis rate was independent of exogenous tyrosine levels. In the three regions studied, the combined stimulatory effects of 8-Br-cyclic AMP and high K+ were additive. CCK-5, CCK-3, CCK-27-33, and CCK-8 (sulphated) enhanced synthesis, CCK-5 being the most potent fragment. The nonsulphated octapeptide had no effect. In all three regions, CCK-5 and high K+ had an additive effect on dopamine synthesis; CCK-5 and 8-Br-cyclic AMP together produced the same enhancement of synthesis as CCK-5 alone. CCK-5 produced similar dose-dependent increases in dopamine synthesis and cyclic AMP accumulation in striatal synaptosomes, and both effects were blocked by the CCK antagonist proglumide.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

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↗
PubMed1986

An amperometric enzyme electrode for monitoring brain glucose in the freely moving rat.

Brain glucose concentration was measured with an amperometric enzyme electrode using glucose oxidase (EC 1.1.3.4) irreversibly adsorbed onto an organic conducting salt. The responses of the electrode and its stability both in vitro and in vivo are described. Parellel changes in brain glucose and blood glucose (measured in samples from an implanted intra-atrial cannula) following injections of insulin are reported.

Animals↗
PubMed1986

The effect of presynaptic receptor stimulation on adenosine 3',5'-cyclic monophosphate concentrations in rat cortical synaptosomes.

Changes in adenosine 3',5'-cyclic monophosphate (cAMP) concentration were measured in cortical synaptosomes. Preincubation with adenosine deaminase reduced cAMP concentration by 45%. Oxotremorine, clonidine, gamma-aminobutyric acid (GABA) and baclofen produced no change in basal concentration. 2-Chloroadenosine and noradrenaline (NA), acting at beta-adrenoceptors, both caused a dose-dependent increase in cAMP; the NA-stimulated increase was depressed by GABA and by baclofen.

2-Chloroadenosine↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

Stimulation of noradrenaline synthesis by the calcium ionophore A23187 and its modulation by presynaptic receptors.

Noradrenaline (NA) synthesis in rat hippocampal synaptosomes is increased by calcium ionophore, A23187, in the presence of calcium. Activation of presynaptic muscarinic, gamma-aminobutyric acidB (GABAB) and alpha 2-adrenergic receptors causes inhibition of the ionophore-stimulated synthesis. The results suggest that different mechanisms mediate the depression by presynaptic receptors of NA release and NA synthesis.

Adenosine Deaminase↗
PubMed1985

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↗
PubMed1985

Low-frequency septal stimulation increases tyrosine hydroxylase activity in the hippocampus.

Rats were chronically implanted with recording electrodes in the dorsomedial subiculum and stimulating electrodes in the septal area. Low-frequency septal stimulation (regular inter-pulse interval = 130 msec) was used over a period of 10 days to drive the hippocampal theta rhythm at 7.7 Hz (a régime shown previously to proactively facilitate acquisition of barpressing and retard its extinction), and high frequency (77 Hz) stimulation was used to block theta rhythm (a régime shown previously to proactively retard acquisition of barpressing and facilitate its extinction). The activity of soluble tyrosine hydroxylase from hippocampus increased in animals killed 15-33 days after the end of the period of 7.7 Hz septal stimulation but not after high-frequency stimulation. Irregular low-frequency stimulation with a mean inter-pulse of 130 msec produced the same effect on tyrosine hydroxylase activity as regular 7.7 Hz theta-driving. The possible relations between the effects of low-frequency septal stimulation on hippocampal tyrosine hydroxylase and on behavior are discussed.

Animals↗