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Biomedical subjects

A Fredriksson

Publications and source records attributed to A Fredriksson.

86 records · Page 5Linked to original sources
PubMed1986

Central noradrenaline depletion antagonizes aspects of d-amphetamine-induced hyperactivity in the rat.

The effects of noradrenaline (NA) depletion upon amphetamine-induced hyperactivity were examined in five experiments. Central NA depletion via either systemic DSP4 or neonatal 6-OHDA antagonised the amphetamine-induced (2 mg/kg SC) increase in rearing behaviour, whereas lesions of the dorsal noradrenergic bundle using 6-hydroxydopamine antagonised the increase in locomotor activity. Peripheral NA depletion following systemic 6-hydroxydopamine to adult rats did not cause any changes in motor activity after acute amphetamine administration. Desipramine, the selective NA uptake inhibitor, blocked the effects of DSP4 upon amphetamine-induced rearing. NA depletion antagonised hyperactivity produced by the 2 mg/kg dose of amphetamine, but not the hyperactivity (rearing or locomotion) effects of amphetamine at 1, 4 or 8 mg/kg.

Animals↗
PubMed1986

The inhibition of the cage-leaving response--a model for studies of the serotonergic neurotransmission in the rat.

It was observed that rats that had been given drugs that enhance serotonergic neurotransmission, e.g. the serotonin releasing compounds p-chloroamphetamine (PCA) and fenfluramine, the MAO-A inhibitors and serotonin releasing agents amiflamine and alpha-ethyltryptamine and the serotonin agonists 5-methoxy-N, N-dimethyltryptamine (5-MeODMT), 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT), m-chlorophenyl piperazine (m-CPP) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969), did not leave their home-cages when the grid-covers were removed in contrast to normal rats who almost immediately left the cages. The association between the serotonin neurotransmission and the inhibitory effect of PCA on the cage-leaving response was indicated by the findings that 1. Serotonin uptake inhibitors (alaproclate and citalopram) antagonized the effect of PCA. 2. High, neurotoxic doses of PCA antagonized the effect of PCA when tested one week after the former administration. The serotonin uptake inhibitor zimeldine counteracted the effect of neurotoxic PCA. 3. Depletion of brain serotonin with p-chlorophenylalanine counteracted the effect of acute PCA. 4. Repeated treatment of rats for 7 days with zimeldine, amiflamine, alpha-ethyltryptamine or clorgyline plus a low dose of PCA counteracted the effect of acute PCA probably due to a functional down-regulation at postsynaptic receptors. Clorgyline or a low dose of PCA by themselves had no effect. 5. Compounds interacting with dopamine or noradrenaline mechanisms, e.g. alpha-methyltyrosine, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP 4), pimozide, remoxipride and prazosin did not antagonize the effect of PCA nor did (+)-amphetamine inhibit the cage-leaving response. None of the serotonin receptor antagonists (cinanserin, ketanserin, metergoline, methysergide, metitepine, mianserin, pirenperone) blocked the inhibition of the cage-leaving response produced by PCA, indicating that the receptors involved may not be of the S1- and S2- types. Observation of the cage-leaving response may be a valuable technique in studies of drugs that enhance the serotonin neurotransmission in the rat brain.

Animals↗
PubMed1985

Increased total activity in the rat after L-tryptophan plus the monoamine oxidase-A inhibitor amiflamine but not after L-tryptophan plus clorgyline.

The effect of pretreatment with either saline or the monoamine oxidase-A inhibitors clorgyline and amiflamine upon the total activity, locomotion and rearing behaviour of the rat induced by various doses of the monoamine precursor L-tryptophan was studied by use of automated activity boxes. Amiflamine (2.5 and 5.0 mg kg-1, i.p.) increased in a dose-dependent manner total activity and to a lesser extent, locomotion when given 60 min before L-tryptophan (100 mg kg-1, i.p.). The increased activity was seen after amiflamine plus either 25 or 75 mg kg-1 L-tryptophan. Rearing behaviour was not affected. Analysis of 5-hydroxytryptamine (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) by high performance liquid chromatography with electrochemical detection indicated that in both frontal cortex and hypothalamus, amiflamine (at both doses) increased 5-HT and reduced 5-HIAA concentrations. Combination of amiflamine with L-tryptophan (100 mg kg-1, i.p.) resulted in a higher 5-HT concentration being found than after amiflamine alone. L-Tryptophan treatment alone did not change 5-HT concentrations but increased 5-HIAA concentrations. Clorgyline, at a dose of either 1 or 5 mg kg-1 i.p. plus L-tryptophan (25 or 100 mg kg-1, i.p.) did not increase total activity, locomotion or behaviour. A number of possible explanations for the differences in the behavioural effects of clorgyline and amiflamine when given with L-tryptophan are discussed. It is concluded that in addition to monoamine oxidase-A inhibition, other pharmacological effects of the drugs, such as 5-HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L-tryptophan.

Animals↗
PubMed1980

The retinol-binding protein.

Vitamin A is transported from its storage site in the liver to the epithelial tissues by a carrier protein, the Retinol-binding protein (RBP). In plasma RBP forms a complex with thyroxine-binding prealbumin. The present article reviews available data on the RBP system. The complete primary structure of RBP has been determined. The plasma concentration of RBP is regulated by the vitamin A status so that in vitamin A deficiency RBP molecules are not secreted from the liver. RBP molecules interact with a cell membrane receptor, probably a protein component present on epithelial cells. Vitamin A is thereby delivered to the cells. The uptake of vitamin A by the cells causes a reduction of the affinity of RBP for prealbumin. The RBP molecules which no longer are able to interact efficiently with prealbumin are excreted through the kidney glomerulus and degraded.

Amino Acid Sequence↗
PubMed1976

Heme compounds in the plasma in small bowel ischemia in the rat.

The early diagnosis of acute mesenteric occlusion presents a difficult problem in abdominal surgery. In a study on rats the relation between graded small bowel ischemia and the concentration of heme compounds in the plasma was investigated. The ischemia was produced by ligation of terminal vessels at the mesenteric margin of the intestine (mesenteric end arcades) or the superior mesenteric artery. Heme compounds were assayed by a benzidine method developed by Crossby et al. The concentration of heme compounds in the plasma was higher in animals with various grades of intestinal ischemia than in animals subjected to laparotomy alone. This increase was noted as early as 4 hours after induction of moderate and severe grade of ischemia. The results indicate that an increase in plasma concentration of heme compounds takes place at an early stage of moderate and severe small bowel ischemia following mesenteric vascular occlusion but not until after 48 hours in mild ischemia. The clinical value of this method has to be tested in a clinical study.

Animals↗
PubMed1975

Renal handling of beta2-microglobulin in experimental renal disease.

Renal extraction and urinary excretion of 125I-labelled beta2-microglobulin was studied in rats. The effect of ischaemic renal injury, experimental pyelonephritis, and unilateral nephrectomy was investigated. The tubular secretion of o-iodohippurate (OIH) was measured for comparison. The urinary excretion was calculated as the ratio between the clearance of protein and the glomerular filtration rate. The glomerular filtration rate was estimated as clearance of polyethylene glycol (PEG 1000). The renal arteriovenous concentration difference was lower for beta2-microglobulin than for PEG 1000 IN ALL THE EXperimental groups. In unilateral renal disease the beta2-microglobulin excretion of the intact kidneys was similar to that of the diseased kidneys. A significant differences was noted only after ischaemic renal injury. The same was found for OIH. After removal of the intact kidneys the excretion of beta2-microglobulin increased about 10-fold in pyelonephritic animals and 2- to 30-fold in animals with ischaemic renal injury. One hour after unilateral nephrectomy in normal animals the ratio increased about 50 per cent. The tubular secretion of OIH did not change noticeably. It is concluded that the glomerular filtration is a main step in the intrarenal catabolism of beta2-microglobin and that its urinary excretion is considerably influenced by a reduction in the functioning kidney mass.

Animals↗
PubMedDate not supplied

Effects of prenatal exposure to tributyltin and trihexyltin on behaviour in rats.

The effects of prenatal administration of tributyltin (1 and 5 mg/kg) and trihexyltin (5 mg/kg) upon the development and behavioural repertoire of rats were studied. The dose levels were selected so as not to induce maternal toxicity. No consistent delay upon occurrence of various maturation markers of the organotin-treated offspring was seen. As adults the tributyltin-treated offspring showed considerable hyperactivity following the initial habituation whereas the trihexyltin-treated offspring showed hyperactivity to a lesser degree. In the spatial learning tasks applied, the radial arm maze and the circular swim maze, tributyltin-treated rats demonstrated a clearly retarded aquisition of the radial arm maze task whereas trihexyltin-treated rats performed as well as the control rats; no differences were obtained in the swim maze task. The tributyltin-treated offspring showed a drastic potentiation of d-amphetamine-induced hyperactivity, whereas trihexyltin treatment induced only a marginal increase.

Animals↗
PubMedDate not supplied

Behavioural effects of prenatal metallic mercury inhalation exposure in rats.

The effects of administration by inhalation of metallic mercury vapour (Hg0) to pregnant rats, approximately corresponding to doses of 0.2 mg Hg0/kg/day (high dose) or 0.07 mg Hg0/kg/day (low dose), on the developmental and behavioural repertoire of the offspring were studied. Exposure occurred during days 11-14 plus 17-20 of gestation. The dose levels were selected so as not to induce maternal toxicity. Maturation variables such as surface righting, negative geotaxis, pinna unfolding, and tooth eruption revealed no differences between Hg0-treated offspring and controls. Tests of spontaneous motor activity showed that the Hg0-treated offspring were hypoactive at 3 months of age but hyperactive at 14 months. In spatial learning tasks the prenatally exposed offspring showed retarded acquisition in the radial arm maze but no differences in circular swim maze. A simple test of learning, habituation to a novel environment (activity chambers), indicated a reduced ability to adapt. These data suggest that prenatal exposure to Hg0 vapour results in similar behaviour changes in the offspring as reported for methylmercury.

Administration, Inhalation↗
PubMedDate not supplied

Prenatal coexposure to metallic mercury vapour and methylmercury produce interactive behavioural changes in adult rats.

Pregnant rats were 1) administered methyl mercury (MeHg) by gavage, 2 mg/kg/day during days 6-9 of gestation, 2) exposed by inhalation to metallic mercury (Hg degrees) vapour (1.8 mg/m3 air for 1.5 h per day) during gestation days 14-19, 3) exposed to both MeHg by gavage and Hg degrees vapour by inhalation (MeHg + Hg degrees), or 4) were given combined vehicle administration for each of the two treatments (control). The inhalation regimen corresponded to an approximate dose of 0.1 mg Hg degrees/kg/day. Clinical observations and developmental markers up to weaning showed no differences between any of the groups. Testing of behavioural function was performed between 4 and 5 months of age and included spontaneous motor activity, spatial learning in a circular bath, and instrumental maze learning for food reward. Offspring of dams exposed to Hg degrees showed hyperactivity in the motor activity test chambers over all three parameters: locomotion, rearing and total activity; this effect was potentiated in the animals of the MeHg + Hg degrees group. In the swim maze test, the MeHg + Hg degrees and Hg degrees groups evidenced longer latencies to reach a submerged platform, which they had learned to mount the day before, compared to either the control or MeHg groups. In the modified, enclosed radial arm maze, both the MeHg + Hg degrees and Hg degrees groups showed more ambulations and rearings in the activity test prior to the learning test. During the learning trial, the same groups (i.e., MeHg + Hg degrees and Hg degrees) showed longer latencies and made more errors in acquiring all eight pellets. Generally, the results indicate that prenatal exposure to Hg degrees causes alterations to both spontaneous and learned behaviours, suggesting some deficit in adaptive functions. Coexposure to MeHg, which by itself did not alter these functions at the dose given in this study, served to significantly aggravate the changes.

Administration, Inhalation↗
PubMedDate not supplied

Changes in behavior and muscarinic receptor density after neonatal and adult exposure to bioallethrin.

Throughout life, mammals are exposed to environmental toxicants, some of which have acute effects on the nervous system. Early, low-dose exposure in combination with later re-exposure and possible interference with normal aging have been little studied. The present study revealed increased susceptibility in adult mice, exposed neonatally to a low dose of the insecticide bioallethrin, to renewed exposure to bioallethrin as adults. Ten-day-old Naval Medical Research Institute male mice received bioallethrin orally (0.7 mg per kg body weight per day for 7 days). When aged 5 months they were given the same dose of bioallethrin by gavage. Twenty-four hours after the last administration, a spontaneous motor activity test revealed significant aberrations in mice exposed both neonatally and as adults to bioallethrin. The density of muscarinic receptors was significantly increased. When aged 7 months, spontaneous behavioral disturbances and muscarinic receptor changes persisted and learning and memory deficits had developed. These results indicate that neonatal exposure to bioallethrin has the potential to increase susceptibility of the adult mouse to a new exposure at a dosage that does not have any effect in animals treated neonatally with vehicle.

Age Factors↗