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Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

At least 325 records · Page 18Linked to original sources
PubMed1981

Effects of acute central and peripheral administration of nicotine on ascending dopamine pathways in the male rat brain. Evidence for nicotine induced increases of dopamine turnover in various telencephalic dopamine nerve terminal systems.

The actions of intraventicular injections and intravenous infusions of nicotine were studied on dopamine stores and turnover in discrete areas of the forebrain of normal male rats. This was done by measuring the decline of the dopamine stores after tyrosine hydroxylase inhibition using alpha-methyl-tyrosine methyl ester (H44/68). The dopamine concentrations in the various telencephalic dopamine nerve terminal systems were measured using the Falck-Hillarp methodology involving quantitative microfluorimetry. The catecholamine concentrations in the anteromedial frontal cortex were measured biochemically using high pressure liquid chromatography combined with electrochemical detection. Intraventricular experiments. The dopamine levels in discrete areas of nuc. caudatus and nuc. accumbens were significantly reduced even with the lowest dose of nicotine (1 microgram/rat). Intraventricular injections of nicotine in a dose of 100 microgram/rat produced significant increases of dopamine turnover in various types of dopamine nerve terminal systems in the nuc. caudatus, nuc. accumbens and tuberculum olfactorium, and following a dose of 10 microgram/rat increases of dopamine turnover were observed in the medial part of the nuc. caudatus. Furthermore, nicotine (100 microgram/rat) significantly increased noradrenaline but not dopamine turnover within the anterofrontal cortex. Intravenous experiments. The dopamine levels were selectively reduced by nicotine (1000 microgram/kg) in the cholecystokinin positive and negative dopamine nerve terminal systems of the nuc. accumbens. On the other hand, dopamine levels in the anteromedial frontal cortex were increased after this dose of nicotine. Intravenous infusions of nicotine (10-1000 microgram/kg) produced dose-related increases of dopamine turnover in the various dopamine nerve terminal systems analysed in the telencephalon. These effects became significant with a dose of 1000 microgram/kg/h. The dopamine terminals in the nuc. caudatus showed a higher sensitivity to intravenous infusions of nicotine, being affected by 10-100 microgram/kg of nicotine. These findings suggest that relatively low dose of nicotine via an activation of central nicotine-like cholinergic receptors can reduce dopamine concentration and increase dopamine turnover in discrete limbic and striatal areas. These actions may in part represent the neurochemical basis for the rewarding actions of nicotine and for nicotine dependence in man.

Afferent Pathways↗
PubMed1980

The mesolimbic dopamine system: evidence for a high amine turnover and for a heterogeneity of the dopamine neuron population.

By means of a new photographic method to quantitate catecholamine fluorescence in tissue sections it has been possible to demonstrate a high dopamine (DA) turnover within the DA cell bodies of the midbrain. The medially located small-sized DA cell bodies of the A10 DA cell group has a very high DA turnover which was significantly different from that found in the laterally located medium-sized DA cell bodies of the A10 cell group. Thus, the mesolimbic DA pathways may be divided into two systems, the medial system having a very high DA turnover in their cell bodies which may reflect a high functional activity in this system.

Animals↗
PubMed1980

Compensatory bilateral changes in dopamine turnover after striatal kainate lesion.

Diseases of the extrapyramidal systems like Parkinson's disease and Huntington's chorea have been closely associated with the basal ganglia. In particular, the prominent symmetrical nigrostriatal dopaminergic systems play an important role in pathogenesis and symptomatology of motor disorders. Biochemical and electrophysiological data indicate a functional relationship between the nigrostriatal pathways on the two brain hemispheres. Unilateral pharmacological manipulations result in short-term changes in contralateral dopamine (DA) release, and surgical lesions on one side lead to long-term alterations in the firing rate of contralateral dopaminergic neurones. We report here the effects of unilateral kainic acid-induced lesions of striatal cell bodies on ipsi- and contralateral striatal DA turnover. We present evidence that morphologically intact dopaminergic neurones on both sides possess compensatory mechanisms which can counteract striatal synaptic asymmetries. Such mechanisms could be responsible at least in part for the maintenance of symmetrical motor behaviour in unilaterally lesioned animals.

Animals↗
PubMed1980

Toluene-induced activation of certain hypothalamic and median eminence catecholamine nerve terminal systems of the male rat and its effects on anterior pituitary hormone secretion.

Subacute exposure to high concentrations (500--1000 ppm) of toluene vapour led to an increase of noradrenaline levels in the subependymal layer of the median eminence (SEL) and to an increase of noradrenaline turnover within the subependymal layer, the paraventricular hypothalamic nucleus and the anterior periventricular hypothalamic nucleus (PV I). Increased dopamine levels in the lateral palisade zone of the median eminence (LPZ) and increased catecholamine turnover within the medial palisade zone (MPZ) were also produced. Measurement of the anterior pituitary hormone secretion showed a significant increase of FSH and delayed increase of corticosterone secretion following toluene exposure.

Animals↗
PubMed1980

Herbicide exposure and tumor mortality. An updated epidemiologic investigation on Swedish railroad workers.

An earlier cohort study of Swedish railroad workers indicated a possible relationship between exposure to herbicides and an increased overall tumor morbidity and mortality. The cohort of 348 individuals has now been followed through October 1978. In this updated analysis of the causes of death among railroad workers, the observed number of tumor deaths was higher than expected, especially among individuals exposed in the earlier years of the study to both amitrol and phenoxy acids. However, the excess tumor mortality among persons exposed to amitrol became more moderate, and the earlier, slightly increased tumor mortality among people exposed to phenoxy acids more pronounced. No specific type of tumor predominated although there were three stomach cancers and three lung cancers. The result of the previous analysis of deaths among these railroad workers has been confirmed as to an excess of tumors, but the aspects of causal relationships to specific agents remain rather unclear, especially since workers exposed to a combination of amitrol and phenoxy acids seem to be the most seriously affected. However, the result, being in agreement with animal data and other epidemiologic studies, suggests a need for the careful handling of amitrol and phenoxy acids as increasingly suspicious carcinogens.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1980

Central monoamine synapses as sites of action for ergot drugs.

The acute and subacute effects of ergot drugs on central monoaminergic mechanisms were studied in the rat. The most significant findings are: 1. After acute treatment, lergotrile and bromocriptine were found to block apomorphine-induced locomotion and rearing, suggesting that these two ergot drugs can block postsynaptic DA receptors within the nucleus accumbens. 2. Several ergot drugs were shown to have high affinity for some 3H-ADTN binding sites. Earlier studies indicate that 3H-ADTN appears to label postsynaptic dopamine receptors located on nerve cells in the striatum. These ergot-sensitive 3H-ADTN binding sites appear not to be linked to the adenylate cyclase system. In addition, bromocriptine, unlike CM 29-712, was found to have a high affinity for 3H-spiperone binding sites in the striatum. 3. Bromocriptine and CM 29-712 increased norepinephrine turnover in periventricular and paraventricular hypothalamic areas, suggesting a blockade of norepinephrine receptors. CM 29-712 also increased DA turnover in the medial palisade zone of the median eminence. 4. Some ergot drugs also had affinity for 5-HT receptor binding sites, possibly reflecting a 5-HT agonistic action in some areas, as shown in behavioral studies. 5. Apomorphine and bromocriptine displaced in vivo 3H-spiperone binding in the hypothalamus, septal area, and substantia nigra, but not in the striatum. 6. Subacute treatment with bromocriptin and CM 29-712 were found to produce two types of changes in behavior: The apomorphine-induced locomotion was enhanced while the chewing and licking activity (stereotypies) was reduced. These behavioral changes may be associated with an increased affinity in the 3H-ADTN binding sites in the striatum. This treatment also produced persistent increases of DA turnover in the tuberculum olfactorium but not in striatum.

5-Hydroxytryptophan↗
PubMed1980

Mecamylamine induced blockade of nicotine induced inhibition of gonadotrophin and TSH secretion and of nicotine induced increases of catecholamine turnover in the rat hypothalamus.

Nicotine treatment of normal male rats and of ovariectomized female rats results in increases of dopamine (DA), noradrenaline (NA) and adrenaline (A) turnover in the hypothalamus, especially within the median eminence. These effects may in part mediate the inhibition of gonadotrophin and TSH secretion produced by nicotine.

Animals↗
PubMed1980

Effects of chronic treatment with l-sulpiride and haloperidol on central monoaminergic mechanisms.

Chronic treatment with l-sulpiride (20 mg/kg, twice daily) and haloperidol (0.2 mg/kg, twice daily) for 2 weeks produced behavioral signs of DA receptor supersensitivity in both the striatum and the nucleus accumbens-tuberculum olfactorium region. Thus, 48 hr after treatment apomorphine-induced locomotion, total activity, and rearing activity was significantly enhanced. These behavioral results were correlated with 10% increases in the number of binding sites for the DA agonist 3H-ADTN and the DA antagonist 3H-spiperone in striatum, but the latter sites appeared to be markedly increased in number in the subcortical limbic region. A marked loss of stereoselectivity was demonstrated in the 3H-ADTN binding site, a change that could also in part be involved in producing the signs of enhancement of DA effector mechanisms observed. A corresponding loss of stereoselectivity was not observed in the 3H-spiperone binding site to which, instead, the (+)-butaclamol had an increased affinity. Haloperidol, but not l-sulpiride, in the doses used produced a further enhancement of degeneration-induced supersensitivity at DA receptor sites.

5-Hydroxytryptophan↗
PubMed1980

Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes.

Various inhibitors were used to study further the mechanism of natural killing and to compare it to lympholysis by cytotoxic T lymphocytes (CTL). The respiratory inhibitors DNP and NaN3 or low temperatures (0 degrees) blocked the cell contact phase of target-effector interaction in the CTL system but not the NK system. The lytic stage was also inhibited by the glycolytic inhibitors, iodoacetate and NaF, in the NK system as previously shown in the CTL system. Dimethylsulphoxide, a dipolar solvent, and cytochalasin B, a microtubule disruptor, inhibited NK target binding. Pre-treatment of Nk cells with glutaraldehyde, a protein cross-linking agent, completely prevented lysis, but not the formation of target-effector conjugates. The lytic phase of NK lysis was inhibited by chloroquine which also inhibited lysosomal enzyme function. Lysosome defective, beige mutant mice were also totally deficient in NK lytic function and this defect could not be restored with cGMP. T-cell and macrophage mediated cytolysis was previously shown to be relatively normal in beige mice. These results suggest that (i) the mechanism of NK cytolysis is a complex, multistep process, and (ii) this process is fundamentally different from that occurring in CTL. A 'stimulus-secretion' model of NK cytolysis is presented in which it is postulated that lysosomal enzymes may be the lytic molecules.

Animals↗
PubMed1980

Effects of chronic treatment with 1-sulpiride and haloperidol on central dopamine turnover evaluated in dopamine cell body and nerve terminal-rich areas.

Catecholamine levels and turnover have been analyzed in DA cell body and in terminal-rich areas of the midbrain, diencephalon, and forebrain 48 hr following a 2-week treatment with l-sulpiride and haloperidol. At this time interval behavioral supersensitivity to DA agonists has been demonstrated. No changes in DA turnover are found in the DA cell body groups A9 and A10 or in various DA terminals of forebrain, with a possible exception for the diffuse type of DA terminals in the tuberculum olfactorium where a reduction of DA turnover rate is observed. In the median eminence of the l-sulpiride-treated group, however, DA turnover increases are observed. It is suggested that the lack of amine turnover changes in most of the DA terminal systems of the brain is related to the development of DA receptor supersensitivity in both striatal and limbic areas, balancing the DA receptor blocking activity of the neuroleptic drugs still present in the tissue of the brain.

Animals↗
PubMed1979

On the role of ascending dopamine systems in the control of voluntary ethanol intake and ethanol intoxication.

Selective lesions of the ascending dopamine pathways were made by bilateral injection of the neurotoxin 6-OHDA (8 micrograms/4 microliters). Catecholamine fluorescence histochemistry revealed a marked degeneration of the ascending mesostriatal and mesolimbic dopamine systems, while the hypothalamic dopamine and noradrenaline nerve terminals were unaffected. After recovery of feeding and drinking behaviors the voluntary ethanol intake was not different from that of the controls. The time of ethanol-induced narcosis and the extent of ethanol-induced hypothermia were not affected. In contrast, in a tilting-plane test conducted two months after the operation, ethanol impaired the performance of the 6-OHDA-treated rats significantly less than that of the controls. This finding suggests a role for the ascending dopamine neurons to the forebrain in the intoxicating effect of ethanol.

Alcohol Drinking↗
PubMed1979

A method to determine dopamine levels and turnover rate in discrete dopamine nerve terminal systems by quantitative use of dopamine fluorescence obtained by Falck--Hillarp methodology.

In tissue sections of regions with evenly distributed dopamine (DA) nerve terminals such as the nucleus caudatus, it is possible to obtain absolute amounts (nmol/g) of DA by means of quantitative microfluorimetrical measurements of catecholamine (CA) fluorescence intensity in the tissue and in DA-containing albumin-agar standards. The values agree well with mass-fragmentographical determinations of DA. The steady-state DA levels of heterogenously innervated areas such as the tuberculum olfactorium determined by quantitative microfluorimetry can be made comparable to the steady-state levels of DA obtained by biochemistry in the entire tuberculum olfactorium by means of a conversion factor which considers the dilution of the DA-containing structures by non-DA-containing nerve cells in the biochemical analysis. This factor is obtained by making biochemical determinations in such regions of untreated animals (e.g. the tuberculum olfactorium). The results of this paper have demonstrated that the histochemical approach not only has a high power of resolution and makes it possible to perform studies on an intact morphological substrate but also allows the determination of DA steady-state (nmol/g) and DA turnover rate (nmol/g x min-1) in discrete DA nerve terminal systems of the brain in absolute amounts.

Analysis of Variance↗