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Biomedical subjects

H Fink

Publications and source records attributed to H Fink.

At least 91 records · Page 5Linked to original sources

Sulpiride blocks postsynaptic dopamine receptors in the nucleus accumbens.

Intra-accumbens injection of sulpiride, tiapride, and metoclopramide antagonized locomotor hyperactivity induced by intraperitoneal administration of apomorphine in rats and measured over the first five minutes after introducing the animal to an open-field cage. Sulpiride was slightly more potent than tiapride which was more than 10 times more potent than metoclopramide and haloperidol. The threshold dose of sulpiride was as low as 0.001 microgram, bilaterally. Intra-accumbens injection of sulpiride also blocked exploratory hypermotility induced by bilateral intra-accumbens injections of apomorphine and picrotoxin. The threshold dose of sulpiride for blocking these two effects was about 0.01 microgram, bilaterally. Sulpiride was more than 10 times more potent than haloperidol in blocking this apomorphine-induced hypermotility. Haloperidol did not influence the picrotoxin hypermotility. The results obtained indicate strong postsynaptic dopamine antagonist properties of sulpiride, tiapride and metoclopramide.

Animals↗

Effect of a novel environment on locomotor hyperactivity of rats induced by apomorphine in the nucleus accumbens.

Bilateral local injections into the nucleus accumbens of apomorphine in doses between 0.125 and 20 micrograms produced a dose-dependent increase of locomotor activity in rats recorded over the first 5-min period after placing the animals in a novel environment 7 min after the injection. Continuous records over consecutive 5-min periods revealed that the locomotor effect of apomorphine (1 microgram, bilaterally) declines rapidly within less than 30 min. Progressively weaker locomotor hyperactivity in the first 5-min periods was observed after prolongation of the interval between intra-accumbens injection of apomorphine and the commencement of testing from 7 to 12, 17 and 22 min, respectively. Since no difference was found between locomotor activity of animals just placed in the novel environment and that of animals already present in this environment for one or more periods of record at fixed times after the injection, it is concluded that exploration does not contribute to locomotor hyperactivity induced by intra-accumbens injections of apomorphine.

Animals↗

Clozapine--a serotonin antagonist?

The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 micrograms), suppressed the LSD effect in the same manner as serotonin antagonists did. Since alpha-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an alpha- adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 micrograms), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.

Animals↗

[Morphological changes in the neurons of the rat nucleus raphe dorsalis following application of 5,7-dihydroxytryptamine. A golgi-rapid-impregnation study].

The effect of stereotactically applicated 5,7-dihydroxytryptamine on the demonstrability of the different neuron types of the nucleus raphe dorsalis of the rat was investigated by means of the Golgi-rapid-impregnation technique. Degenerative changes could be demonstrated on the polygonal neurons, only. Typical variations of the dendritic structure was shown on the fusiform neurons. The pyriform neuron typ was not affected.

5,7-Dihydroxytryptamine↗

An automated micropipet especially designed for use with the oil-well technique.

A high-precision microprocessor-controlled micropipetting unit which is applicable for serial enzyme or substrate microdeterminations with the oil-well technique is described. Positioning of the reaction wells, pipetting of microliter and submicroliter volumes, as well as measurements of incubation times are performed automatically following an adjustable present program.

Autoanalysis↗

LSD-potentiated apomorphine hypermotility: a model for differentiating antipsychotic drugs.

The model of LSD-potentiated apomorphine hypermotility (LPAH) in rats in comparison to apomorphine-induced hypermotility (AH) was used to investigate typical and atypical neuroleptics by analyzing complete dose response curves. Haloperidol (0.06 mg/kg) induced a parallel shift to the right of both the AH and LPAH dose response curves indicating dopaminolytic properties without any serotonolytic effect. Chlorpromazine (0.5 mg/kg) caused a mixed inhibitory effect on the LPAH, whereas the AH was not affected, probably due to the variety of actions at different transmission systems. Clozapine (0.125 mg/kg) antagonized the LSD effect indicating serotonolytic properties, whereas an additive influence on the AH might be caused by its cholinolytic properties. Sulpiride (10 mg/kg) potentiated both the AH and the LPAH, probably due to presynaptic dopaminergic mechanisms. Two conclusions can be drawn: (1) The results agree with and support the idea of a serotonergic modulation of the (predominant) mesolimbic dopaminergic system in the induction of locomotor effects. (2) The model of LPAH is useful to clearly differentiate typical from atypical neuroleptics, and to obtain information whether there is a primary involvement of dopaminergic or serotonergic mechanisms.

Animals↗

Biochemistry of the ageing rat lens. I. Lens wet weight and lens dry weight with respect to sex differences.

The lens wet weight differed from the age of 136 days: the male lenses were significantly heavier than the female lenses. The dry weight, in percent of the lens wet and dry weight, of the water-soluble proteins decreased and the dry weight of the water-insoluble proteins increased during ageing. At an age of 870 days, when the dry weight curves crossed each other, the lens contains equal amounts of water-soluble and water-insoluble proteins. At the end of the life expectancy, the relation between the water-soluble and water-insoluble moiety was 0.7 for the rat and 3.5 for the bovine lens. The dry weight percent of the water-soluble proteins was lower for the female lens, whereas that of the water-insoluble proteins was higher for the female lens. The male lens, on the contrary, showed a higher percentage of water-soluble and a lower percentage of water-insoluble proteins with increasing age. The ratio R of the dry weight of water-soluble to water-insoluble proteins was, from the age of 429 days, lower for the female lens. During ageing, the proportion of the lens-water was higher for the male lens.

Age Factors↗

[Estimating age from biochemical data of the lens (author's transl)].

The age of the rat can be estimated more accurately from the enzyme pattern of the lens of its eye than from the eye's wet weight. The two together result in a degree of accuracy of from - 13% to 15% for approximately two-thirds of all individual estimations. The observations cover 92% of the natural life expectancy of the rat. The principal enzyme used in estimating its age is aldolase; glucose-6-phosphate-dehydrogenase provides no relevant data.

Aging↗

LSD mescaline and serotonin injected into medial raphe nucleus potentiate apomorphine hypermotility.

Microinjections of LSD (0.05 microgram), mescaline (0.5 microgram) and serotonin (10 microgram) into the medial raphe nucleus of rats resulted in a strong potentiation of apomorphine (1 mg/kg i.p.)-induced hypermotility. The potentiating effect of LSD or serotonin was suppressed by simultaneous injections of methysergide (0.05 microgram) or cyproheptadine (0.05 microgram) into the medial raphe nucleus. The same doses of LSD injected into the dorsal raphe nucleus and of LSD and mescaline injected into the nucleus accumbens failed to influence locomotor activity, whereas injections of higher doses of LSD and mescaline into the nucleus accumbens inhibited spontaneous and apomorphine-stimulated locomotor activity. It is concluded that the potentiating effect of systemically administered low doses of hallucinogens was triggered by preferential actions on the serotonergic system in the medial raphe nucleus.

Animals↗

Computer-aided calculation of dose response curves in behavioral pharmacology by using a nonlinear regression procedure.

In a variety of behavioral pharmacological experiments drug induced graded responses can be recorded even if one animal can be tested only once. In this case the analysis of dose response relationships will be accompanied with theoretical and practical problems additional to those known for dose response curves in single subjects as well as for the all-or-none type of responses. An experimental design was considered where one quantitatively measurable response of each animal tested contributed to an average dose response relationship. Use was made of a four parameter model capable of fitting s-shaped dose response curves over the whole feasible dose range for solving this nonlinear regression problem. Two examples, the dose dependent increased locomotor activity induced by apomorphine and the inhibited locomotor activity after pimozide treatment, were given to demonstrate the use of the method described and to direct the reader's attention to the wide range of its possible applications.

Animals↗

Effects of atypical antidepressants on LSD potentiated apomorphine hypermotility in rats.

The model of LSD potentiated apomorphine hypermotility [5] was used to classify different atypical antidepressants (danitracen, mianserin, cyproheptadine) and pizotifen. All drugs have been shown to inhibit specifically the locomotor activity potentiating effect of LSD in a low dosage range (0.1-0.5 mg/kg i. p.) without influencing the apomorphine effect. Since there is some evidence that the effect of LSD is due to the inhibition of the activity of serotonergic raphe neurons, the marked antagonizing effects of danitracen, mainserin, cyproheptadine and pizotifen are regarded to be an expression of pronounced antiserotonin activity.

Animals↗

A simplified enzymatic assay for the determination of acetylcholine and choline in discrete structures of rat brain.

Acetylcholine and choline were determined in discrete structures of the rat brain by using a simplified radioenzymatic method. Animals were killed by microwave irradiation. The time for killing was controlled by estimating the activity of acetylcholine esterase. After extracting acetylcholine and choline from the tissue by formic acid/acetone the amines were separated by thin-layer-chromatography and radioenzymatically labelled as described by SAELENS et al. The radiolabelled acetylcholine was extracted by sodium tetraphenylboron/hexanone. After washing the organic phase with buffer the radiolabelled acetylcholine was measured in a liquid scintillation counter. The contents of acetylcholine and choline were determined in nucleus accumbens septi, olfactory tubercle and striatum and compared with literature data.

Acetylcholine↗

Scopolamine-induced hypermotility in rats is mediated via a dopaminergic system.

To clarify the relation between cholinergic and dopaminergic transmission systems involved in locomotor effects the influence of dopaminergic drugs on scopolamine hypermotility was investigated. Scopolamine and apomorphine in locomotor stimulant doses showed additive effects. Apomorphine in a dose acting on presynaptic dopaminergic receptors decreased the scopolamine hypermotility markedly. Haloperidol antagonized both scopolamine and apomorphine hypermotility in an apparently competitive way. Sulpiride potentiated scopolamine locomotor effect. Additionally, it was shown that LSD potentiated scopolamine hypermotility as well as apomorphine hypermotility. The results suggest in connection with literature data that locomotor effects of drugs affecting cholinergic transmission may by mediated by a dopaminergic system.

Animals↗

The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man.

In blind studies the effects of a new alpha-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum triglyceride levels were determined. In addition, safety studies were performed. BAY g 5421 induced a statistically significant, in part dose-dependent inhibition of the postprandial increase of blood glucose- and serum insulin levels. The reduction of the postprandial increase of serum triglyceride levels was variable. Routine blood chemistry and hematology tests have revealed no adverse side effects; but the application of the drug was frequently associated with intestinal effects, such as flatulence and diarrhea, which were substrate (carbohydrate) and, in part, dose-dependent.

Administration, Oral↗

The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on postprandial blood glucose, serum insulin, and triglyceride levels: dose-time-response relationships in man.

In a double-blind quadruple cross-over study the effect of a new alpha-glucosidase inhibitor (BAY g 5421) on postprandial blood glucose, serum insulin, and serum triglyceride increases was tested in 24 male healthy volunteers. They received before a standardized breakfast 50, 100, or 200 mg of BAY g 5421 or a placebo per os. The dose-time-response relationships were calculated and the drug tolerance was assessed. There was a statistically significant inhibition of the postprandial increases of the blood glucose, serum insulin, and triglyceride values. Further analysis showed no dose-dependent effect of the drug on the blood glucose values, whereas the serum insulin and triglyceride values were affected in a dose-dependent fashion. The maximal inhibitory effect on the serum insulin levels occurred 69 min after breakfast and on the serum triglyceride levels 104 min after breakfast. One hundred and 200 mg of BAY g 5421 were equally inhibitory-effective on the serum insulin levels, whereas the highest dose used was markedly more effective on serum triglyceride values than lower doses. Based on these results, a dosage of 100--200 mg of BAY g 5421/meal is recommended for clinical trials in metabolic diseases.

Administration, Oral↗