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Biomedical subjects

O Magnusson

Publications and source records attributed to O Magnusson.

At least 19 recordsLinked to original sources
PubMed2000

A9 and A10 dopamine nuclei as a site of action for effects of 8-OH-DPAT on locomotion in the rat.

The 5-hydroxytryptamine (5-HT) 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was applied locally (0-5 microg bilaterally) into either the substantia nigra (A9) or the ventral tegmental area (A10) of adult male Wistar rats, and 10 min later spontaneous motor activity was observed in an open field ( approximately 0.5 m(2)) for 30 min. The rate of dopamine synthesis was estimated in neostriatal areas, the amygdala, and the prefrontal cortex, by measuring the accumulation of DOPA, following inhibition of cerebral decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015). The A10 application of 8-OH-DPAT resulted in an increase in all aspects of spontaneous motor activity in the open field. A9 application of 8-OH-DPAT produced a stereotyped forward locomotion, characterized by a modest decrease in total horizontal activity, almost complete inhibition of rearing activity and an increase in proportion forward locomotion along the perimeter of the open-field arena. The injection of 8-OH-DPAT into the A9 was accompanied by an increased neostriatal DA rate of synthesis, whereas the A10 injection was followed by a decreased DA rate of synthesis in the amygdala and in the prefrontal cortex. It is concluded that mesencephalic dopaminergic mechanisms are involved in the stereotyped forward locomotion characteristically seen after systemic administration of the 5-HT(1A) receptor agonist 8-OH-DPAT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Expression of CD1d in the duodenum of patients with cow's milk hypersensitivity.

CD1 cell surface glycoproteins represent a family of non-major histocompatibility complex (MHC) encoded antigen-presenting molecules. All members of the CD1 family appear to mediate the recognition of microbial or endogenous lipid and glycolipid antigens. The recognition of CD1d by a unique subset of natural killer (NK) T cells that leads to rapid production of large amounts of both type 1 and type 2 cytokines can be augmented by some synthetic glycolipids. Because of the proposed role of such CD1d-restricted T cells in immunoregulation, we hypothesized that CD1d molecules participate in mucosal immune responses in patients with gastrointestinal symptoms owing to food hypersensitivity. Patients of that category represent a heterogeneous group in which poorly defined immunological mechanisms are believed to contribute to disease pathogenesis. The expression of CD1 in duodenal biopsy samples from six patients with verified intolerance to cow's milk and six healthy controls was studied by immunoperoxidase staining of cryostat sections using a panel of mouse monoclonal antibodies (MoAbs) specific for CD1a, b, c, and d. Large numbers of CD1d positive cells were found in the lamina propria of all the patients, both during the symptomatic and the asymptomatic periods, whereas healthy controls were virtually devoid of CD1d expression in the duodenum. The localization of CD1d positive cells corresponded to areas where B cells, plasma cells and dendritic cells (DC) were present. A positive correlation was found between the numbers of CD1d(+) and CD19(+) cells in the lamina propria. In contrast to previous reports, no CD1d expression was found on the epithelial cells. Although less numerous than CD1d(+) the CD1c(+) cells were also present in all the patients and in five out of six controls. No staining for CD1a or CD1b was detected in the duodenal biopsy samples from any of the subjects. The exclusive presence of CD1d in the duodenal lamina propria of the patients with cow's milk hypersensitivity might suggest the participation of these molecules in the pathogenesis of allergic reactions to food.

Adult↗
PubMed1999

Synergism between 5-HT1B/1D and 5-HT1A receptor antagonists on turnover and release of 5-HT in guinea-pig brain in vivo.

The effects on 5-HT turnover (5-HIAA/5-HT ratio) and extracellular 5-HT and 5-HIAA levels (in vivo microdialysis in freely moving animals) were analysed in guinea-pig brains following the 5-HT1B receptor antagonist, GR 127935 [N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide], or the 5-HT1A receptor antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), administered alone or in combination. GR 127935, injected alone, increased 5-HT turnover with maximal effects approximately 50% above the control levels in the four brain regions examined (hypothalamus, hippocampus, striatum and frontal cortex). GR 127935 significantly increased extracellular concentrations of 5-HT and 5-HIAA in frontal cortex (40%), whereas 5-HIAA, but not 5-HT, was elevated in striatum (20-30%). WAY-100635 did not significantly change 5-HT turnover but caused a small significant increase in the extracellular 5-HT and 5-HIAA concentrations in both striatum and frontal cortex. The combined treatment with GR 127935 and WAY-100635 resulted in an increased 5-HT turnover reaching maximal effects of 70-90% above the control values in all brain regions tested and produced a significant elevation of striatal and frontal cortex extracellular 5-HT (40% and 60%, respectively) and 5-HIAA (60% and 70%, respectively) concentrations. The synergistic effect of the two receptor antagonists on the 5-HT turnover and the terminal release of 5-HT indicate somatodendritic 5-HT release and stimulation of inhibitory 5-HT1A receptors at this level. Extracellular 5-HIAA seems to be a better marker than 5-HT itself for the evoked 5-HT release when the reuptake mechanism is intact.

Animals↗
PubMed1999

In vivo intrinsic efficacy of the 5-HT1A receptor antagonists NAD-299, WAY-100,635 and (S)-(-)-UH-301 at rat brain monoamine receptors.

The receptor-mediated control of brain monoamine synthesis was used to examine the in vivo intrinsic efficacy of the 5-HT1A receptor antagonists NAD-299, S(-)-UH-301 and WAY-100,635. The rate of monoamine synthesis was estimated by measuring the accumulation of DOPA and 5-HTP in the ventral neostriatum and the ventral hippocampus in rats pretreated with an inhibitor of cerebral aromatic L-amino acid decarboxylase. S(-)-UH-301 (2.0-32.0 micromol kg(-1)), but not WAY-100,635 (0.08-1.2 micromol kg(-1)), produced a decreased 5-HTP accumulation in the neostriatum and in the hippocampus. The administration of NAD-299 (0.75-12.0 micromol kg(-1)) resulted in a slight increase in neostriatal, but not hippocampal, 5-HTP accumulation. Neostriatal DOPA accumulation was decreased by S(-)-UH-301, whereas treatment with WAY- 100,635 resulted in an increase. NAD-299 did not affect neostriatal DOPA levels. There were no effects by any of these agents on DOPA levels in the ventral hippocampus. It is concluded that S(-)-UH-301, but not WAY-100,635 or NAD-299, displays intrinsic efficacy at brain 5-HT1A and DA D2/3 receptors, whereas WAY-100,635 behaves as a DA D2/3 receptor antagonist. By this comparison, NAD-299 appears to be the most selective and specific 5-HT1A receptor antagonist.

5-Hydroxytryptophan↗
PubMed1997

Influence of 5-HT1B/1D receptors on dopamine release in the guinea pig nucleus accumbens: a microdialysis study.

To clarify whether serotonin (5-HT) 5-HT1B/1D receptors are involved in dopamine (DA) release, extracellular levels of DA were monitored by in vivo microdialysis during various conditions. 5-HT (10 microM) alone, and together with the 5-HT1B/1D receptor antagonist. GR127935 (10 microM), or the 5-HT1B/1D agonist, sumatriptan (1 microM), were perfused into the nucleus accumbens of freely moving guinea pigs. A 10-fold increase in the extracellular concentration of DA was obtained during administration of 5-HT alone. The 5-HT-induced DA elevation was not significantly affected by co-administration of sumatriptan (MANOVA; P > 0.05) but markedly attenuated by coperfusion of GR127935 (MANOVA; P = 0.02). Neither GR127935 nor sumatriptan, when administered alone, significantly affected extracellular DA levels. These results suggest that, in the DA-rich nucleus accumbens, 5-HT1B/1D receptors are not involved in the modulation of DA release during normal tonic or basal conditions but may take part in the regulation of DA release when synaptic 5-HT levels are very high.

Analysis of Variance↗
PubMed1996

Effects of intermittent and continuous subchronic administration of raclopride on motor activity, dopamine turnover and receptor occupancy in the rat.

With the purpose of finding means to circumvent the marked pharmacokinetic differences of raclopride between rats and man, the effects of intermittent and continuous administration of raclopride were compared in rats. Intermittent administration of raclopride via subcutaneous injections resulted in a prompt increase of dopamine (DA) turnover and decrease of motor activity but these effects were of short duration, probably due to rapidly decreasing raclopride DA D2 receptor occupancy. In contrast, but similar to schizophrenic patients on raclopride treatment, stable plasma raclopride levels and a steady DA D2 receptor occupancy above 70% were produced in the caudate-putamen and nucleus accumbens/olfactory tubercle, when raclopride was administered continuously via minipumps at daily doses above 2 mg/kg. Tolerance to the acute effects of raclopride on DA turnover and locomotion was found with both routes of administration but it was more marked with continuous administration. At continuous raclopride administration, tolerance to the effects of raclopride on DA turnover and spontaneous motor activity as well as supersensitivity to amphetamine-induced motor activity occurred when 70% or more of DA D2 receptor sites were occupied, i.e. the same degree of receptor occupancy as found in patients given therapeutic doses of raclopride.

Amphetamine↗
PubMed1995

Time course of bromocriptine induced excitation in the rat: behavioural and biochemical studies.

The aim of the present study was to further investigate the behavioural and biochemical pharmacology of the directly acting dopamine (DA) receptor agonist bromocriptine (BRC). BRC produced an initial depression of locomotion followed after about an hour by a weak but significant locomotor stimulation. The stimulation was potentiated by concomitant administration of the D1 agonist SKF38393. Ex vivo biochemical determinations indicated that reductions in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels occurred in the striatum after BRC injection without a significant change in DA levels, indicating a reduced DA turnover. An increase in 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) levels occurred in the striatum leading to a significant increase in turnover (i.e. ratio of 5HIAA to 5HT). Noradrenaline concentrations increased in the striatum. In the cortex, sharp falls in HVA and DOPAC levels without a corresponding change in DA were observed. While there was no significant change in noradrenaline levels in this brain region, an increase in 5HIAA, but not in 5HT, levels occurred. These changes indicate an increase in 5HT turnover (ratio of 5HIAA to 5HT). In vivo dialysis indicated that extracellular levels of DA, DOPAC and HVA in the striata of freely moving rats were sharply reduced for at least 6 h after injection. In vitro binding studies showed that BRC exhibited high (Ki values in low nanomolar range) affinities for DA D2A, D2B, D3, alpha 1 and alpha 2 adrenergic receptors together with unexpectedly high affinity (about 1 nM) for 5HT1A receptors. The data indicate that the initial behavioural depression and later locomotor stimulation induced by BRC are accompanied by a sharp monophasic fall in striatal extracellular DA levels as indicated by dialysis studies. Since the behavioural stimulation was augmented by concomitant D1 receptor stimulation, the data suggest that the reduced DA turnover is influencing the amount of DA available to stimulate postsynaptic D1 receptors. However, the biochemical studies indicated that BRC has a high affinity for 5HT1A receptors and affects the turnover of 5HT in the brain. Thus, the behavioural effects of BRC may depend not only on effects on the DA system but also on 5HT systems.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Neurochemical effects of prolonged treatment with remoxipride as assessed by intracerebral microdialysis in freely moving rats.

1. At three microdialysis sessions, dialysates were collected from the striatum of the same rats. 2. Microdialysis session 1. A single s.c. injection of remoxipride (40 mumol/kg), resulted in increased dialysate concentrations of dopamine, DOPAC and HVA. 3. Microdialysis session 2. Continuous administration of remoxipride (8.6 mumol/rat/day) for 14 days, using mini-osmotic pumps, produced maintained elevated levels of dopamine, DOPAC and HVA. 4. Microdialysis session 3. A challenge dose of remoxipride (40 mumol/kg s.c.), given to the rats after a 48-hour wash-out period following the continuous remoxipride treatment, increased the dialysate concentrations of dopamine, DOPAC and HVA to similar extent as at dialysis session 1. 5. It is concluded that after long-term treatment of remoxipride, an adaptation of the basal state of the DA system appears to take place, implying a lowering of basal DA release and DA metabolism. However, the capacity to respond with increased DA release and DA metabolism to renewed remoxipride treatment is retained, indicating little, if any, tolerance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Distribution of D1- and D2-dopamine receptors, and dopamine and its metabolites in the human brain.

Densities and distribution of D1-dopamine and D2-dopamine receptors were investigated in vitro using [3H]SCH 23390 and [3H]raclopride in receptor binding assays and autoradiography on human post mortem whole hemisphere slices to serve as anatomical correlates to PET studies using [11C]SCH 23390 and [11C]raclopride. In addition, the levels of dopamine and its metabolites were determined by HPLC in various brain regions. Both dopamine receptor subtypes, as well as dopamine, HVA and DOPAC, were primarily found in the basal ganglia. Very high densities of D1-dopamine receptors were found particularly in the medial caudate nucleus, whereas D2-dopamine receptors were evenly distributed throughout the caudate. The densities of D1- and D2-dopamine receptors were similar in the caudate nucleus and the putamen, whereas there were 4 to 7 times higher densities of the D1- than of the D2-dopamine receptors in several limbic and neocortical regions. The receptor distribution in the autoradiographic study was consistent with that demonstrated in the living human brain using [11C]SCH 23390 and [11C]raclopride.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Tissue and microdialysate changes after repeated and permanent probe implantation in the striatum of freely moving rats.

Neurochemical and morphological effects of repeated microdialysis or permanent microdialysis probe implantations in striatum were studied. The extracellular levels of dopamine did not change between a first and a second probe insertion separated by 2 weeks or at a third dialysis session 2 days later. The 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were similar at the first and second microdialysis session, but decreased at the third. Probes implanted permanently for 2 weeks clogged, and the recovery varied markedly after insertion of new probes. Tyrosine hydroxylase-stained dopamine fibers appeared unaffected after all dialysis sessions, although some swollen fibers were observed surrounding the probes. No change in the glial fibrillary acidic protein staining was seen immediately after the first dialysis session, although 2 weeks later gliosis was observed. After the second and third dialysis a diffuse gliosis was observed, while a glial barrier was seen surrounding the permanently implanted probes. Immediately after the first dialysis session enlarged laminin-stained blood vessels were seen, whereas repeated probe implantation also increased the blood vessel density. Thus, chronic in vivo microdialysis with permanently implanted probes is limited by severe technical problems and marked tissue changes. On the other hand, repeated probe insertion in the same brain site appears to be acceptable for performing chronic microdialysis studies in the same subject, provided neurochemical and morphological changes are taken into consideration.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Temporal studies of the inhibition of voluntary ethanol intake in the rat induced by intermittent ethanol treatment and some long term neurochemical consequences.

Male rats were injected with ethanol (groups 3 and 5; 2.0 g/kg i.p.) or saline (groups 2 and 4) once a week for 52 weeks. The rats had access to ethanol as a voluntary choice for 24 h either once 6 days after the injection (groups 2 and 3) or twice 3 and 6 days after the injection (groups 4 and 5). At the beginning of the treatment ethanol injections inhibited voluntary ethanol intake if tested 6 days later (groups 3 and 5), but a tolerance developed to this inhibition. During tolerance development the rats in group 5 also drank less ethanol on day 3 than on day 6. No corresponding behaviour was seen in group 4. Thus part of the tolerance was a gradual reduction of the duration of inhibition. During the evaluation period (25 weeks) after the treatment, ethanol exposure (20 weeks) consisted of a continuous choice between ethanol and water. Of different ethanol concentrations both ethanol-injected groups (3 and 5) took the same voluntary dose of ethanol independent of the offered concentration. After 5 weeks without ethanol all rats were killed and a number of neurochemical variables were determined. Compared with almost unexposed rats (group 1) changes were seen in inositol phospholipid breakdown, muscarinic binding sites in hippocampus, noradrenaline concentrations in frontal cortex, hippocampus and hypothalamus, dopamine concentration in frontal cortex and 5-hydroxytryptamine concentration in hypothalamus. In most cases the largest changes were seen in group 5. None of the variables had a constant relation to ethanol intake in the total population. However, significant correlations were found in some of the groups.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Suppression of conditioned avoidance behavior by the local application of (-)sulpiride into the ventral, but not the dorsal, striatum of the rat.

The local application of (-)sulpiride, 200 ng side-1, into the nucleus accumbens produced a suppression of conditioned avoidance behavior in male rats, 10 and 90 min after injection. The decrease in avoidance behavior was accompanied by a decrease in motor activity, as evidenced by changes in the number of intertrial crosses. When injected into the dorsolateral neostriatum, or the amygdala, (-)sulpiride produced a suppression of conditioned avoidance behavior at the 90-min time interval only. Considering diffusion from the injection site, as indicated by an increase in local dopamine turnover [(DO-PAC + HVA) DA-1], the effects obtained in the dorsolateral neostriatum, and possibly also the amygdala, 90 min after injection could be due to diffusion to the nucleus accumbens. The local application of (-)sulpiride into the posterior neostriatum, or into the prefrontal cortex, produced no statistically significant effect on conditioned avoidance behavior 10 or 90 min after injection. It is concluded that the performance of conditioned avoidance behavior in the rat is critically dependent on an intact dopaminergic neurotransmission in the nucleus accumbens or adjacent areas of the ventral striatum.

Amygdala↗
PubMed1990

Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy.

Seventy-one women who had a proctocolectomy for ulcerative colitis (n = 41) or Crohn's disease (n = 30) were interviewed in the follow-up clinic about gynaecological problems and fertility. All women were examined by an independent gynaecologist and abnormalities of the internal genital tract were registered. Forty-nine per cent (35/71) of the women had a distressing vaginal discharge after proctocolectomy, compared with 9% (6/71) before surgery. At the gynaecological examination 45% (32/71) had a heavy vaginal secretion with- out any signs of an acute vaginal infection. In 68% (30/44) fluid retention in the vagina was associated with a caudally firmly fixed and dilated posterior vaginal fornix. Twelve per cent (8/66) of the women reported dyspareunia before surgery. After surgery, 27% (18/66) complained of this symptom. Fertility was significantly reduced after surgery since only 37% (10/27) of the women who attempted to become pregnant succeeded within 5 years follow-up. The corresponding figure before surgery was 72% (39/54). Those who conceived went through pregnancy and parturition without any incident, 6 of 21 delivered by caesarean incision. In conclusion, conventional proctocolectomy in women will result in distressing vaginal discharge, and dyspareunia in a considerable proportion of the patients. The operation also seems to decrease their chances of becoming pregnant.

Adult↗