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R Ortmann

Publications and source records attributed to R Ortmann.

At least 37 records · Page 2Linked to original sources

Effect of beta-adrenoceptor agonists on apomorphine-induced turning in rats.

The beta-adrenoceptor agonists clenbuterol, salbutamol and formoterol were found to inhibit apomorphine-induced turning behavior in rats with unilateral nigrostriatal lesions. The inhibitory effect of clenbuterol was antagonized by (-)-propranolol, but unaffected by practolol (which does not cross the blood-brain barrier), indicating a central localization of the beta-adrenoceptors mediating the inhibitory effect. A dopamine-releasing activity of clenbuterol did not seem to be responsible for the effect, because known dopamine-releasing agents (amphetamine, methylphenidate) did not antagonize apomorphine-induced turning behavior. Furthermore alpha-methyl-p-tyrosine pretreatment did not prevent the inhibitory effect of clenbuterol. Since L-5-hydroxytryptophan did not mimic the inhibitory effect of clenbuterol, it was concluded that the inhibition of turning behavior is not mediated by the interaction of clenbuterol with the serotonin system. The finding that clenbuterol depressed locomotor activity in the same dose range as it inhibited apomorphine-induced turning tentatively suggests that clenbuterol inhibits apomorphine-induced turning behavior by its central beta-adrenoceptor mediated sedative action.

Adrenergic beta-Agonists↗

The 5-HT syndrome and the drug discrimination paradigm in rats: application in behavioral studies on the central 5-HT system.

The use of two behavioral tests, the 5-HT motor syndrome in rats and the drug discrimination paradigm for behavioral analysis of the central 5-HT system are discussed. The motor syndrome induced by L-5-HTP in rats is a simple test, allowing the identification of inhibitors of the 5-HT reuptake system and MAO-A. 5-HT-antagonists and 5HT-agonists can also be detected. The degree of selectivity of 5-HT agonists for the 5-HT system can be determined by the use of specific 5-HT-antagonists, or by testing drugs in MAO-inhibited or 5,7-DHT-lesioned animals. The advantages of the drug discrimination paradigm are mainly the low doses of training drugs needed, the objectivity of the test (no observer involved) and the possibility to test for both agonistic and antagonistic activity in the same animals. The drug discrimination paradigm may also contribute to the behavioral differentiation between drugs interacting with 5-HT1, 5-HT2 and possibly tryptamine receptors.

5-Hydroxytryptophan↗

Phenylethylamine-induced stereotypies in the rat: a behavioral test system for assessment of MAO-B inhibitors.

Stereotyped sniffing behavior together with forepaw padding--defined as the beta-phenylethylamine (PEA) syndrome--is induced by MAO-B inhibitors in rats injected with 30 mg/kg IP PEA. The comparison of the abilities of the MAO-B inhibitors to induce the syndrome and to inhibit MAO-B in rat brain homogenates indicated that at least 75% of MAO-B activity in rat brain had to be inhibited to induce the PEA syndrome. A good correlation was found between the abilities of MAO-B inhibitors to induce the behavioral syndrome and to increase levels of PEA in rat brain. Specific MAO-A inhibitors potentiated the behavioral effect of the MAO-B inhibitor deprenyl, while they did not induce the syndrome themselves or only at very high doses. Inhibitors of the reuptake of 5-HT or noradrenaline were inactive under the described experimental conditions. This behavioral test system seems to be a useful in vivo screening test in rats for detecting compounds with strong MAO-B inhibiting activity.

Animals↗

[Relation between the ellipsis and the horizontal skull contour in man and various primates].

The values of the human skull circumference measured in the plane of its greatest length and that of the ellipsis determinated by the semiaxis a, the half largest length of the skull, and the semiaxis b, the half largest breadth, prove a high correlation which is neither dependent on the skull form nor size. The difference between the circumference of the skull and the ellipsis amount only a few % and correlates to the skull form. The areas of intersection of the skull and the area of the ellipsis correspond entirely. Samples of non-human primates show the skull in all Haplorhini being also adjustet to the area of the ellipsis, but the correlation is not so good as in human objects and is depending on the species. The morphological difference is caused by the skull contour-lines passing under and over the ellipsis to the same amount without changing the quantitative ratio of the skull area to the ellipsis area.

Adult↗

[Analysis of human petrous bone for the purpose of measurements and observations of the course of collagen in polarized light].

The values of the superior angle, height and cross sections of the petrous bone show a considerable variation which seems to be almost independent of the form and size of the skull. The cross section of the bone resembles more the positive part of a sinus curve than a triangle. The theoretical superior angle calculated by using cross section and height has a mean value of 87 degrees +/- 6 degrees. The values of height and cross sections are correlated in non-linear equation curve, the formula of which can be calculated as y = 0,59 x2 + 105,3. The values of height and the superior angle have a negative correlation and follow a tangent function. The values of the superior angle correlated to the cross section area as far as they belong to the same height also follow a tangent function. The angle between the plane of the greatest height of the petrous prism and the occlusal surface shows a mean of 32 degrees. The alignment of the collagen fibers analyzed by polarized light indicates a bending stress of the petrous bone. The histological findings and the simple correlations of the measured values suggest that form and structure of the petrous bone is adjusted by biomechanical factors.

Adolescent↗

[Subarticular spongiosa and its relation to the remaining internal structure of the calcaneus in the human].

The subarticular cancellous bone of the human calcaneus has been investigated in sixty nine cases of known age and sex. In addition eleven calcanei without corresponding informations were used. The three forms of cancellous bone and their threedimensional junctions were analysed by means of the dental burr. It is shown an age bound transformation of the roundmeshed cancellous bone into tubular structures and finally into bone plates or an trabecular network. A tubular construction is presumed as intermediate stage changing by osteolysis into bone plates or trabecular meshwork. The conception of the trajectorial structure presented by Gierse (1976) is more differentiated and enlarged. Considering the calcaneus the normal osteoporosis of old age can be understood to be an age controlled exactly adjusting process. The findings of wide spaced an enlarged cancellous bone elements in a few elder individuals is thought to be a secondary adaptation after preceding normal reduction. Histologic and biometric investigations of this subject will be following.

Adolescent↗

Septo-hippocampal system: target for substituted benzamides.

Effects of the substituted benzamide, and of oxiperomide on DA receptors and on Da-related behaviors were the object of the study. The benzamides were practically inactive on DA-sensitive adenylate cyclase and on in vitro [3H] spiperone binding (in the absence of sodium ions). However, all of them inhibited in vivo [3H] spiperone binding in various rat brain regions; this in vivo effect was especially apparent in hippocampus and septum. In frontal cortex, the benzamides (with the exception of metoclopramide) produced only a partial inhibition of [3H] spiperone binding. Such inhibition also occurred in the striatum with sulpiride and tiapride. The results suggest that substituted benzamides are DA antagonists due to their ability to inhibit in vivo [3H] spiperone binding. The lack of agreement between in vivo and in vitro tests is also discussed.

Adenylyl Cyclases↗

Effect of yohimbine and its diastereoisomers on clonidine-induced depression of exploration in the rat.

The effects of yohimbine, rauwolscine and corynanthine on clonidine-induced depression of exploration (ambulation and rearing) in the rat were investigated. Yohimbine and rauwolscine antagonized clonidine-induced hypoactivity in a dose-range of 0.3 - 3 mg/kg i.p. By contrast, corynanthine was found to lack such an effect up to ten times higher doses. These results are in agreement with the reported differential affinity of these drugs for the alpha 2-adrenoceptors respectively and suggest the involvement of alpha 2-receptors in the mediation of depressant effect of clonidine. The antagonism of clonidine-induced hypoactivity appears, therefore, to provide a suitable in vivo measure of preferential alpha 2-adrenoceptor blocking activity of drugs.

Animals↗

Correlations between different measures of antiserotonin activity of drugs. Study with neuroleptics and serotonin receptor blockers.

The antiserotonin properties of a series of neuroleptics, 5-HT-receptor blockers and some adrenoceptor antagonists were investigated in several in vivo test systems (L-5-HTP syndrome and 5-HT-paw edema in the rat) and in an in vitro test (isolated rat uterus preparation). The results were compared to the results obtained with these drugs in an in vivo 3H-spiperone binding assay in the rat. The computations of the relative ED50 (or IC50) values obtained in different test procedures showed that the ability of drugs to bind to 5-HT receptors labelled by 3H-spiperone in the rat frontal cortex correlates fairly well with their potencies to inhibit the L-5-HTP syndrome or 5-HT-induced rat pawedema (Spearman rank correlation coefficient, r = 0.80 and 0.79 respectively, n = 22). In an in vitro test (rat uterus) the estimated 5-HT-receptor blocking potency of the tested drugs did not, however, correlate with any of the in vivo measures used for this purpose. The results suggest, therefore, that for the determination of central antiserotonin effects of drugs in the rat, functional in vivo tests (L-5-HTP syndrome or 5-HT-induced rat paw-edema) could yield about the same information as the specific, in vivo 3H-spiperone binding assay. The 5-HT-receptor type mediating the behavioral responses to L-5-HTP is tentatively defined as a 5-HT2 receptor.

5-Hydroxytryptophan↗

Experimentally induced supersensitivity of neocortical neurons to microiontophoretically administered serotonin.

Central serotonergic fiber systems of the rat were selectively lesioned by intraventricular injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At various times thereafter, the sensitivity of rostral cortical neurons to microiontophoretically administered serotonin (5-HT) was compared in groups of lesioned and sham-operated animals pretreated with the 5-HT uptake inhibitor CGP 6085. Twenty-four hours after the injection of 5,7-DHT, at which time the cortical 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were both reduced by 40%, there was no significant difference in the sensitivity of cortical neurons to 5-HT. However, 3 days after such treatment, when the cortical 5-HT and 5-HIAA levels were reduced by 52% and 53% respectively, pronounced supersensitivity to 5-HT was noted. The depressant action of 5-HT on neuronal firing was potentiated with regard to both maximal firing depression and duration of the firing inhibition. A similar potentiation of the 5-HT responses was observed 7 days after lesioning. Supersensitivity thus appears to develop between 1 and 3 days after the injection of 5,7-DHT. Seven days after lesioning, the sensitivity of rostral cortical neurons to gamma-aminobutyric acid was unchanged compared to that observed in sham-operated animals.

5,7-Dihydroxytryptamine↗

Supersensitivity to L-5-hydroxytryptophan after 5,7-dihydroxytryptamine injections in desmethylimipramine- and nomifensine-pretreated rats: behavioral evidence for postsynaptic supersensitivity.

The behavioral syndrome induced by L-5-hydroxytryptophan (L-5-HTP) in rats was used to study the supersensitivity to L-5-HTP and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) which develops after unilateral intracerebroventricular (ICV) injections of 200 microgram 5,7-dihydroxytryptamine (5,7-DHT). Pretreatment of the animals with a combination of desipramine and nomifensine was found to protect dopamine neurones better than desipramine alone. Maximal behavioral supersensitivity to L-5-HTP and 5-MeODMT was found as early as 24 h after injection of the neurotoxin, even in the presence of the specific 5-HT uptake inhibitor CGP 6085 A, or the MAO-A inhibitor clorgyline. The results indicate that a quickly occurring postsynaptic event contributes to the development of behavioral supersensitivity after ICV injections of 5,7-DHT.

5,7-Dihydroxytryptamine↗

Interaction of beta-adrenoceptor agonists with the serotonergic system in rat brain. A behavioral study using the L-5-HTP syndrome.

The effect of beta-adrenoceptor agonists on the behavioral effect of L-5-HTP in rats and mice was studied. All beta-agonists potentiated the behavioral syndrome elicited by L-5-HTP. However no indication for a correlation between their potencies to stimulate peripheral beta-receptors and their potencies to enchance L-5-HTP effect was found. The potentiating effect of salbutamol in rats was intensified by the MAO A inhibitor clorgyline, completely inhibited by (+/-)-propranolol and partly inhibited by WB-4101, while practolol was without effect. Lesions of 5-HT pathways by i.c.v. injections of 5,7-DHT impaired the potentiating effect of salbutamol in rats. In contrast, 6-OHDA lesions or alpha-methyl-p-tyrosine pretreatment were without effect. A central site of action of salbutamol is suggested by the fact that it intensified L-5-HTP effects also after i.c.v. administration. Therefore the results suggest that salbutamol facilitates 5-HT transmission in rat brain probably via stimulation of central beta receptors.

5,7-Dihydroxytryptamine↗

The effects of 5-HT uptake- and MAO-inhibitors on L-5-HTP-induced excitation in rats.

The behavioural syndrome caused by L-5-HTP in rats was used for the study of effects of selective 5-HT uptake inhibitors and inhibitors of MAO on central 5-HT receptors. A good correlation was found between the relative potencies of drugs in inhibiting the 5-HT uptake in the rat brain and in intensifying L-5-HTP-induced behavioural stimulation. The potentiation of the L-5-HTP syndrome by the MAO inhibitors correlated with the inhibition of the A- but not of the B-form of the brain monoamine oxidase. In rats treated with the maximally inhibiting dose of a 5-HT uptake inhibitor, MAO inhibitors were still able to increase the intensity of the L-5-HTP syndrome, while the combination of maximal doses of two 5-HT uptake inhibitors did not produce a more intense syndrome than that produced by one 5-HT uptake inhibitor alone. The L-5-HTP-induced behavioural syndrome in rats seems to afford an experimental model allowing the quantification and characterization of the interaction of drugs with serotonin metabolism in the brain.

5-Hydroxytryptophan↗

Vidian neurectomy: neuroanatomical considerations and a report on a new surgical approach.

If conventional treatment fails, vidian neurectomy is a viable alternative for therapy of chronic rhinitis with recurrent polyposis of the nose and sinuses. From a neuroanatomical point of view beneficial and adverse effects of this surgical procedure are discussed. According to our own investigations and experiences, vidian neurectomy should be performed together with clearing out of the sinuses in every case. Beginning with this precondition a new surgical approach was developed: the vidian nerve is detected through a transethmoidal route in the pterygoid canal at the bottom of the sphenoid sinus and dissected using the operation microscope.

Chronic Disease↗

Phosphorylated derivatives of phloretin inhibit cyclic AMP accumulation in neuronal and glial tumor cells in culture.

The potencies of polyphloretin phosphate, di-4-phloretin phosphate, 4-phloretin phosphate and phloretin to inhibit the stimulation of cAMP accumulation by prostaglandins, isoproterenol and adenosine were studied in 2 clonal cell lines of CNS origin. The sequence of potency to inhibit PGE1 effects was the same in neuroblastoma (N4TG3) and human astrocytoma cells (1321N1): di-4-phloretin phosphate greater than polyphloretin phosphate greater than phloretin greater than 4-phloretin phosphate. The inhibition of PGE1 stimulated cAMP accumulation by the most prostaglandin-specific inhibitor di-4-phloretin phosphate was rapidly established after its addition, fully reversible after a 30 min preincubation period and independent of the presence of calcium. Kinetic studies of the inhibition of PGE1 effects by di-4-phloretin-phosphate suggest a different type of inhibition in 1321N1 and N4TG3 cells.

Calcium↗