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Biomedical subjects

A Dresse

Publications and source records attributed to A Dresse.

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

Electrophysiological effects of ethanol on monoaminergic neurons: an in vivo and in vitro study.

Monoaminergic neurons have been shown to play a role in both the intoxicating and chronic effects of ethanol. We present here the results of a study about the acute effects of ethanol on serotonergic raphe nucleus, noradrenergic locus coeruleus, and dopaminergic ventral tegmental area. These nuclei were investigated electrophysiologically by recording the spontaneous firing rate of single neurons using glass microelectrodes, both in vivo in chloral hydrate anesthetized rats and in vitro in brain slices. Ethanol was perfused intravenously at a rate ranging from 0.2 mg/kg/min to 0.2 g/kg/min in vivo, and at concentrations between 10(-8) M and 1 M in vitro. We observed that each monoaminergic nucleus had its own pattern of responses to acute ethanol perfusion, and that high and low concentrations have different actions, suggesting a biphasic effect. For example, in slices, ethanol concentrations higher than 10 mM induce an excitation in most raphe and ventral tegmental area neurons, and an inhibition of firing in locus coeruleus neurons. The results were comparable in the in vivo model, but much more heterogenous. We conclude that the effect of ethanol on the monoaminergic neurons is specific of the type of neuron, and that a biphasic effect is commonly found.

Animals↗
PubMed1990

Dopamine and acetylcholine release in thalamus of non-parkinsonian and parkinsonian subjects.

A study of neurotransmitter release has been performed on human brain biopsies obtained during the course of a therapeutic neurosurgical procedure. The electrically evoked-release of 3H-dopamine and 3H-acetylcholine was studied on slices from the thalamus of two parkinsonian and two non-parkinsonian subjects. Electrical stimulation of the non-parkinsonian thalamus increased the dopamine release but had no effect on acetylcholine release. This characteristic response had been previously observed in the normal rat thalamus. In contrast, the parkinsonian thalamus responded with a sharp increase in acetylcholine release without concomitant increase in dopamine release indicating the possible existence of an inhibitory control effect action of dopamine on acetylcholine release as seen in rat striatum.

Acetylcholine↗
PubMed1989

Galanin decreases the activity of locus coeruleus neurons in vitro.

A brain slice preparation was used to examine the effects of galanin on the spontaneous firing rate of locus coeruleus noradrenergic neurons. Galanin (10(-9)-10(-7) M), added to the bath, inhibited the firing of 14 out of 19 neurons in a concentration-dependent manner. The observed effect was quite variable, ranging from 20 to 100% at 10(-7) M. Experiments performed in low-Ca2+, high-Mg2+ medium also showed a significant inhibition by galanin (10(-7) M) in three out of five neurons, which suggests that the peptide acts directly.

Animals↗
PubMed1989

Electrophysiological effects of neurotensin on dopaminergic neurones of the ventral tegmental area of the rat in vitro.

The effects of neurotensin on the spontaneous firing rate of presumed dopaminergic neurones of the ventral tegmental area of the rat, were studied in a slice preparation of brain by extracellular single-cell recordings. Bath-applied neurotensin excited all cells which were studied (N = 25). This effect was concentration-dependent; the threshold was 10(-10) M and maximal activation (about 30 spikes/10 sec) was obtained with 10(-6) M. The EC50 (half-maximal effective concentration) was roughly estimated at 35 nM. The action of neurotensin was mimicked by neurotensin 8-13 (N = 6), but not neurotensin 1-8 (N = 6). It persisted in low-calcium, high-magnesium solutions (N = 5) and therefore probably resulted from a direct activation of neurotensin receptors. The responses to neurotensin were long-lasting (30-60 min after a 10 min 10(-7) M infusion) and exhibited little tachyphylaxis. Dose-response curves to the dopaminergic agonist BHT920 showed that, during the infusion of 10(-7) M neurotensin, dopaminergic autoreceptors of some neurones were less sensitive than in control conditions. This was not a non-specific effect produced by the excitation, since it was not observed during the infusion of another excitant, N-methyl-D-aspartate (NMDA). These results show that neurotensin potently activates presumed dopaminergic neurones in the ventral tegmental area in vitro; it may also decrease the effectiveness of the autoreceptors of some neurones.

Adrenergic alpha-Agonists↗
PubMed1989

[Study of new brain peptides using genetic engineering methods].

Using the methods of molecular biology, we have been able to clone 5 rat brain specific cDNAs coding for brain specific proteins. The partial sequencing of the first of those clones gave no homology with the genes contained in Genebank and EMBL data bank. In the future, we intend to look for a possible effect of those brain specific proteins on the neuronal activity of rat brain neurons.

DNA, Circular↗
PubMed1988

Action of rilmenidine on locus ceruleus and dorsal raphe cells in vivo and in vitro.

The effect of rilmenidine (S 3341) and clonidine on the firing rate of locus ceruleus (LC) and dorsal raphe (DR) cells was studied in vivo after systemic and microiontophoretic administration. The effect of the 2 drugs was also studied in vitro on brain slices containing LC cells. Rilmenidine and clonidine inhibited the firing of LC and DR neurons. Complementary experiments performed with yohimbine and prazosin demonstrated that the effect of LC is related to an agonistic action on alpha 2 somatodendritic receptors, whereas the effect observed on DR cells is indirect. On LC cells, clonidine is 30 to 60 times as potent as rilmenidine. These observations may be related to less sedative effects of rilmenidine than of clonidine.

Action Potentials↗
PubMed1988

Influence of food on tianeptine and its main metabolite kinetics.

The influence of a test meal on the absorption and disposition of tianeptine (Stablon), a new antidepressant, was investigated in 12 healthy subjects in a two-way, randomized, open cross-over study. Single 12.5-mg oral doses of tianeptine were administered following a night of fasting or immediately after a standardized breakfast. When subjects received tianeptine under fasting conditions the lag time before absorption onset, and the time of the maximum plasma concentration were 0.55 +/- 0.26 hours and 1.29 +/- 0.29 hours, respectively. The maximum plasma concentration was 322 +/- 44 ng/mL, and the total area under the curve 994 +/- 248 ng/hr/mL. When tianeptine was given at the end of the meal, several significant changes were found for tianeptine kinetic parameters; the lag time increased by 0.3 hour and the maximum plasma concentration was lowered (decreased by 25%) and occurred later (tmax increased by 0.5 hour). However, no significant change was found in the area under the plasma concentration-time curve. The trend and extent of changes in the MC5 metabolite parameters were similar to those observed for the parent drug. Absorption of tianeptine is slightly delayed and slowed down without modification of its extent when tianeptine is given at the end of a meal. These slight changes are not clinically relevant for an antidepressant administered three times a day. Despite the changes observed, tianeptine may be given at meal times to improve compliance with treatment.

Adult↗
PubMed1988

Pimobendane (UD-CG 115 BS) in the treatment of severe congestive heart failure. An acute haemodynamic cross-over and double-blind study with two different doses.

1. We compared the effects of two doses (5 and 10 mg) of oral pimobendane (UD-CG 115) on haemodynamics in eight patients suffering from chronic congestive heart failure. The two doses were given according to a randomized cross-over double-blind protocol; haemodynamics and plasma levels of pimobendane and its main metabolite UD-CG 212, were determined 1, 2, 3, 5, 7, 9, 11 and 12 h after each dose. 2. Both doses significantly improved the left and right ventricular functions of these patients, with a peak action 3 h after drug intake and long duration (more than 12 h). A significant dose-effect relationship was observed only for pulmonary wedge pressure and right atrial pressure. Significant correlations were found between UD-CG 212 plasma levels and cardiac index (r = 0.54, P less than 0.05), and pulmonary wedge pressure (r = 0.74, P less than 0.001); no correlation was found between these haemodynamic variables and pimobendane plasma levels. 3. One patient developed a transient drop in blood platelets together with a cutaneous rash, while three others had a transient and mild decrease of thrombocytes. 4. In conclusion, pimobendane improved right and left ventricular functions in severe heart failure. Both doses (5 and 10 mg) were effective. The higher dose induced marked improvement of the haemodynamic variables but the difference between doses was only significant for right atrial and pulmonary wedge pressures.

Aged↗
PubMed1988

Pimobendane (UD-CG 115 BS) in chronic congestive heart failure. Short-term and one-month effects of a new inotropic vasodilating agent.

We studied the effects of oral administration of pimobendane on hemodynamics, blood gas levels, the renin-angiotensin system, and plasma catecholamines in 11 patients who were affected by severe chronic congestive heart failure. Following the administration of 5 mg, the cardiac index increased from 2.0 +/- 0.2 to 2.5 +/- 0.2 L/min/m2 (p less than 0.01), and the pulmonary wedge pressure decreased from 28 +/- 3 to 17 +/- 4 mm Hg (p less than 0.01). The maximal changes were noted five hours after intake of the drug. In spite of a significant decrease in arterial oxygen pressure (PaO2) (from 81 +/- 4 to 67 +/- 5 mm Hg; p less than 0.05), a significant increase in the oxygen delivery index was seen (from 322 +/- 32 to 436 +/- 38 ml/min/m2; p less than 0.01). The patients who were submitted to long-term treatment (5 mg twice daily) and who were reassessed after at least one month exhibited an improved cardiac index from 1.9 +/- 0.2 to 2.5 +/- 0.1 L/min/m2 (p less than 0.01), as well as a decreased pulmonary wedge pressure from 26 +/- 2 to 14 +/- 4 mm Hg (p less than 0.01). The norepinephrine levels were significantly reduced after one month (from 1,496 +/- 185 to 678 +/- 95 pg/ml; p less than 0.01), whereas the plasma renin activity was not. One patient died suddenly during the one-month follow-up period. With the exception of one case, which was also treated with heparin, a transient cutaneous rash and a drop in the level of blood platelets were observed, pimobendane was well tolerated. This new inotropic and vasodilating drug thus seems to have promise for the treatment of chronic congestive heart failure.

Administration, Oral↗
PubMed1988

Cloning and partial sequencing of a new rat brain specific cDNA.

In order to find brain specific transcripts in a pUC13 cDNA library prepared from rat brain cytoplasmic poly(A)+ RNAs, the following steps were observed: 1. Randomly chosen cDNA clones from the brain library were screened by radiolabelled single stranded cDNAs (sscDNAs) prepared from liver, spleen, kidney and intestine mRNAs. 2. The brain clones containing genetic information shared with the peripheral organs were discarded. 3. After hybridization of the remaining clones with radiolabelled sscDNAs prepared from rat brain poly(A)+ RNAs, 210 possibly brain specific clones were selected. 4. Plasmids containing cDNA of each of these clones were purified and after estimation of their cDNA sizes, clones containing inserts of at least 500 base pairs (bp) were used as radiolabelled probes against rat brain, liver, spleen, kidney and intestine poly(A)+ RNAs spotted onto nitrocellulose filters (dot blot analysis). 5. By using this screening procedure, several brain specific clones were obtained. One of them (clone III 25) is presently subjected to sequencing in M13 phage. 6. A computer analysis of the partial sequence so far obtained gives no significant homology to the 15.000 genes contained in Genebank and EMBL data bank. It seems therefore that we have isolated a new brain specific cDNA coding for a not yet described peptide.

Animals↗
PubMed1988

Electrophysiological effects of tianeptine on rat locus coeruleus, raphe dorsalis, and hippocampus activity.

Electrophysiological studies were performed in order to compare the influence of tianeptine and clomipramine on the firing rate of central locus coeruleus noradrenergic neurons, raphe dorsalis serotoninergic neurons, and hippocampus CA1 pyramidal cells. The interaction of tianeptine and clomipramine with the response of CA1 cells to iontophoretically applied 5-HT or GABA was also investigated. The i.v. perfusion of tianeptine decreased the firing rate of locus coeruleus neurons (ID50 = 1.74 +/- 0.2 mg/kg), did not modify the firing rate of raphe dorsalis neurons, and increased the firing rate of CA1 pyramidal cells (ED50 = 0.68 +/- 0.17 mg/kg). The tianeptine inhibiting dose 50 for noradrenergic neuron firing rate was 2.5 times higher than the activating dose for hippocampus pyramidal cells, and 6 times higher than the inhibiting dose for selective noradrenaline uptake inhibitors as desipramine. In comparison, the i.v. infusion of clomipramine decreased the firing rate of locus coeruleus, raphe dorsalis, and CA1 neurons. The iontophoretic application of tianeptine did not modify the response of CA1 cells to 5-HT or GABA but decreased the recovery time after 5-HT and GABA. The iontophoretic application of clomipramine potentiated the response of CA1 cells to 5-HT but not to GABA and increased the recovery time after 5-HT and GABA. Tianeptine appears to have an original electrophysiological profile in agreement with an increase in serotonin uptake: this profile distinguishes tianeptine from classical antidepressants such as clomipramine.

Action Potentials↗
PubMed1987

Inhibition of pentagastrin-stimulated gastric acid secretion and plasma levels of the new histamine H2-receptor antagonist ramixotidine dihydrochloride (CM 57755) in human volunteers.

The new competitive histamine H2-receptor antagonist, ramixotidine 2 HCl (CM 57755), has been tested in healthy male volunteers for its ability to inhibit pentagastrin-stimulated gastric acid secretion. In the first study, in 8 subjects, pentagastrin 6 micrograms.kg-1 was injected s.c., 90 min after the following 4 oral treatments given in random order at weekly intervals: placebo, 100, 200 and 400 mg CM 57755. Gastric contents were collected over 15-min periods during the 2 h after pentagastrin stimulation. In a second, similar study, 8 subjects received placebo, 0.5 and 1.0 g CM 57755 and 800 mg cimetidine, 120 min before a 2 h i.v. infusion of 6 micrograms.kg-1.h-1 pentagastrin. Cumulative gastric secretion in placebo-treated subjects was 46 +/- 14 and 62 +/- 11 mmol H+.2 h-1 (mean +/- SD), respectively, in the first and second studies. It was significantly reduced only after 400 mg CM 57755 in the first study. In the second study either dose of CM 57755 and cimetidine caused a significant reduction in gastric acid secretion. Average plasma levels of ramixotidine were dose-related after 0.2 and 1.0 g and ranged from 0.3 and 1.6 micrograms/ml, respectively, at 60 min to 0.5 and 3.7 micrograms/ml at 180 min. The peak cimetidine level averaged 3.6 micrograms/ml at 150 min. Individual CM 57755 plasma levels throughout the test period were fairly consistent with the inhibition of cumulative gastric acid secretion scored concurrently in each subject. No subjective side-effects attributable to the treatments were reported, and no abnormal findings were seen in the ECG or in laboratory tests.

Adult↗
PubMed1987

Electrophysiological and microiontophoretic studies with buspirone: influence on the firing rate of central monoaminergic neurons and their responsiveness to dopamine, clonidine or GABA.

The influence of an i.v. perfusion of buspirone on the firing rate of central monoaminergic neurons was studied in rats anaesthetized with chloral hydrate. Buspirone increased the firing rate of A10 dopaminergic neurons and blocked the inhibitory effect of iontophoretically applied dopamine on these neurons. A slight attenuation of the inhibitory effect of iontophoretically applied GABA was also observed. Buspirone increased the firing rate of locus coeruleus (LC) noradrenergic neurons and induced an attenuation of the inhibitory effect of iontophoretically applied clonidine. A slight attenuation of the inhibitory effect of iontophoretically applied GABA was also observed. Furthermore buspirone was a very potent inhibitor of the firing rate of dorsal raphe (DR) serotonergic neurons. It is concluded that activation of A10 neurons by buspirone is due to blockade of dopaminergic autoreceptors and that activation of LC neurons is related to blockade of alpha-2 autoreceptors. The significance of the interaction with gabaergic inhibition is unclear. The mechanisms involved in the inhibition of DR neurons remain to be investigated.

Animals↗
PubMed1987

Effect of rolipram, a phosphodiesterase inhibitor and potential antidepressant, on the firing rate of central monoaminergic neurons in the rat.

Rolipram is a potent phosphodiesterase inhibitor, active in classical pharmacological tests used in the screening of antidepressants (AD). In contrast with classical AD, rolipram does not block the reuptake of monoamines, but its action on the metabolic degradation of cyclic AMP may enhance adenylate-cyclase linked catecholaminergic and serotonergic transmission. Biochemical studies showed that rolipram induces various modifications in the turnover of monoamines but the net effect of these modifications on the electrical activity of monoaminergic neurons remained to be elucidated. Thus, the influence of rolipram on the firing rate of central locus coeruleus (LC) noradrenergic neurons, mesolimbic (A10) dopaminergic neurons and dorsal raphe (DR) serotonergic neurons was investigated. When rolipram was perfused into the jugular vein, it produced a long-lasting excitatory effect on LC neurons, a prolonged but usually partial inhibitory effect on A10 neurons and no consistent effect on DR neurons. The action of rolipram on monoaminergic neurons contrasts with that of most classical and new AD in which the electrical activity of LC and/or DR neurons decreases.

Action Potentials↗
PubMed1986

Influence of the alpha-2 agonist oxaminozoline (S3341) on firing rate of central noradrenergic and serotonergic neurons in the rat. Comparison with clonidine.

The firing rate of central locus coeruleus (LC) noradrenergic neurons and dorsal raphe (DR) serotonergic neurons was recorded in rats anaesthetized with chloral hydrate. The iontophoretic application or the i.v. perfusion of S3341, a new antihypertensive drug or clonidine decreased the frequency of discharge of LC neurons. Depending on the mode of administration clonidine was 54-63 times more potent than S3341. The selectivity of action of both drugs on alpha-2 vs. alpha-1 adrenoceptors was confirmed using yohimbine and prazosin: yohimbine completely blocked the inhibitory effect of S3341 or clonidine while prazosin did not prevent this effect. S3341 and clonidine regularly reduced the firing rate of DR neurons during i.v. perfusion but not during iontophoretic application. From these experiments is it concluded that S3341 and clonidine have a direct inhibitory effect on LC neurons via stimulation of alpha-2 autoreceptors and that both drugs have an indirect inhibitory effect on DR neurons, probably via impairment of noradrenergic transmission. Clinical studies show that S3341 induces much less sedative side effects than clonidine. In view of the great difference in the potency of these drugs to inhibit the firing rate of monoaminergic neurons which are known to be involved in sleep mechanisms, it is possible that the electrophysiological effects reported here relate to the sedative effects of these drugs.

Adrenergic alpha-Agonists↗