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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 36 (1981), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Deacetylation of melatonin to 5-methoxytryptamine (5-MT) in vitro and in vivo was investigated in rat liver and brain tissue, using a gas chromatographic-mass spectrometric 5-MT assay method. In vitro incubation of liver but not brain (hypothalamic, mesencephalic) slices with melatonin led to a concentration-dependent formation of small amounts of 5-MT; the conversion being 0.3–0.8%. In vivo administration of melatonin resulted in a dose-dependent formation of 5-MT in small quantities in the liver. The time course showed a peak maximum within 0.5 h, with a rapid decline; the half-life being about 1 h. 5-MT could be detected in both the blood and the hypothalamus after in vivo injection of melatonin. The time course of 5-MT in the blood was similar to that in the liver, but 5-MT could only be detected in the hypothalamus after large doses shortly after the melatonin injection. MAO had to be inhibited both in the in vitro and in vivo experiments in order to recover 5-MT, indicating that formed 5-MT is normally rapidly metabolised by MAO. It is concluded that a small fraction of melatonin can be converted to 5-MT by deacetylation (by aryl acylamidase) in the liver in vivo, constituting a minor pathway. Such a pathway could not be demonstrated in the brain. Trace amounts of 5-MT previously reported to be present in various tissues could originate from deacetylation of melatonin in the liver and possibly some other peripheral organs known to contain the deacetylating enzyme. The present results indicate that peripherally formed 5-MT, a psychoactive compound, is unlikely to have any effect on brain function under normal circumstances.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 19 (1972), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The uptake-storage properties and synthesis of noradrenaline, and fluorescence morphology of adrenergic nerves which have been allowed to regenerate for 4 weeks after a chemical sympathectomy produced by 6-hydroxydopamine have been investigated in mouse iris and atrium. The regenerated nerve terminals displayed a lower formaldehyde-induced fluorescence intensity whereas the non-terminal axons exhibited a stronger fluorescence intensity and a more beaded appearance compared with mature nerves. The endogenous noradrenaline concentration after 6-hydroxydopamine was 30% in iris and 45% in atrium compared to control values. Recovery of [3H]noradrenaline uptake was found to be more rapid than that of endogenous noradrenaline concentration after the 6-hydroxydopamine treatment. [3H]Noradrenaline uptake in regenerating and adult mature nerves both obeyed Michaelis-Menten kinetics having identical Km values. There was a close correlation between [3H]noradrenaline uptake and nerve density of adrenergic nerves regenerated after 6-hydroxydopamine. These results show that [3H]noradrenaline uptake is a better index for the number of regenerated nerve terminals than is the endogenous noradrenaline concentration. The retention of [3H]noradrenaline taken up and accumulated in vitro was about the same in regenerated and mature nerves, although a slight tendency to less effective retention was observed in the regenerated nerves. Subcellular distribution studies showed that relatively less [3H]noradrenaline was recovered in the microsomal fraction after 6-hydroxydopamine treatment. The formation of 14C-labelled catecholamines from [14C]DOPA was higher in regenerating nerves than indicated by the endogenous noradrenaline concentration but lower than that indicated by the [3H]noradrenaline. It is concluded that the regenerating nerves contain less endogenous noradrenaline than adult mature nerves and that the uptake mechanism develops promptly, whereas the development of the storage mechanism lags behind.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 21 (1973), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —Intravenous injection of a large dose of 6-hydroxydopamine (100 mg/kg) to adult rats caused a significant and long-lasting reduction (about 30 per cent) of the in oirro uptake of [3H]NA in the cerebral cortex and spinal cord, while no changes were seen in the hypothalamus. The endogenous NA in whole brain was similarly reduced (about 20 per cent). Fluorescence histochemistry revealed catecholamine accumulations which are degenerative signs, induced by 6-hydroxydopamine, in axons of the dorsal NA bundle innervating the cerebral cortex. It is concluded that the blood–brain barrier in adult rats is not completely protective with respect to the neurotoxic action of systemically injected 6-hydroxydopamine, which can produce degeneration of a significant number of NA nerve terminals in the cerebral cortex and spinal cord. Previous studies have shown that 6-hydroxydopamine caused a permanent and selective degeneration of a large number of central NA nerve terminals when injected systemically up to 1 week after birth, due to an incompletely developed blood-brain barrier. This barrier for 6-hydroxydopamine develops between the 7th and 9th day after birth (Sachs, 1973). In the present study 6-hydroxydopamine was found to cause a small transient reduction in [3H]NA uptake in cerebral cortex of rats between 9 and 28 days of age, while in older rats the damage produced by 6-hydroxydopamine was long-lasting. Thus, the NA nerves ascending to the cerebral cortex seem to possess a regenerative capacity to a 6-hydroxydopamine-induced degeneration up to about 28 days postnatally, but which later disappears or is markedly retarded.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 8 (1967), S. 288-296 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The histochemical fluorescence method of Falck and Hillarp for the demonstration of catecholamines and certain tryptamines, e.g. 5-hydroxytryptamine is based on the principle that these amines can be condensed with formaldehyde to yield strongly fluorescent 6,7-dihydroxy-3,4-dihydroisoquinolines and 6-hydroxy-3,4-dihydro-β-carbolines respectively. The investigation here reported presents the fluorescence characteristics and relative fluorescence yields for formaldehyde treated biogenic monoamines and certain related compounds enclosed in a dried protein layer. The fluorescence properties of some synthetic 6,7-substituted-3,4-dihydroisoquinolines and 3,4-dihydro-β-carbolines are given, and the fluorescence characteristics in relation to the molecular structure are discussed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 24 (1970), S. 1-6 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present paper describes a method for the determination of small amounts of noradrenaline using the histochemical fluorescence method of Falck and Hillarp. The noradrenaline present in the organ or tissue piece to be determined is extracted by osmotic shock treatment. This extract is used as incubation medium for an iris from a rat pretreated with reserpine and nialamide. This treatment empties the adrenergic nerves of their endogenous noradrenaline content. During the incubation, noradrenaline present in the extract will be taken up and accumulated in the adrenergic nerves of the iris by the axonal “membrane pump”. After the incubation the iris is prepared as a stretch preparation, dried and exposed to formaldehyde gas according to the method of Falck and Hillarp for the histochemical demonstration of noradrenaline. The formaldehyde-induced fluorescence of noradrenaline present in the adrenergic nerves is quantified microfluorimetrically. Irides from rats pretreated in the same way and incubated in media with known concentrations of noradrenaline are used as standards. Using this procedure, rat iris and ciliary body were found to contain 5 ng and 3 ng noradrenaline respectively. These values were in good agreement with those obtained by an enzyme assay of noradrenaline. The great advantage of the method is the extreme sensitivity and 1 ng can very well be determined. The specificity, reproducibility and the limitations of the method are discussed.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Neonatal ; 6-Hydroxydopamine ; Desipramine ; Amfolenic acid ; Dopamine ; d-Amphetamine ; Methylphenidate ; Hyperactivity ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA, 50 μg on day 1 after birth) caused a marked hyperactivity when the rats were tested as adults. These rats also showed severe DA depletions in striatum and nucleus accumbens. Pretreatment with the noradrenaline (NA) uptake inhibitor desipramine provided protection against NA depletion in frontal cortex and nucleus accumbens. Pretreatment with DNA uptake inhibitors, amfolenic acid or GBR 12909, before 6-OHDA, provided full protection against DA depletion but produced marked NA depletion in frontal cortex. These rats did not demonstrate any degree of hyperactivity. Low doses ofd-amphetamine (0.25 mg/kg SC) or methylphenidate (1 mg/kg SC) reversed the hyperactivity in DA-depleted rats but increased motor activity in vehicle-treated and NA-depleted rats. Higher doses ofd-amphetamine (1 mg/kg) or methylphenidate (4 mg/kg) produced potentiated levels of locomotion but attenuated levels of rearing in DA-depleted animals. The results further suggest the utility of the neonatal DA lesion in rats as a potential animal model for derivation of therapeutic agents that may be efficacious in the treatment of the hyperkinetic syndrome.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A method is described which combines the histochemical fluorescence technique of Falck and Hillarp with isotope measurements in the same pieces of tissue. Tissue pieces incubated in isotope solutions were treated for fluorescence microscopy and examined. They were then removed from the microscopical slides, and the radioactivity determined. It was shown that NA1 content and estimated fluorescence intensity were well correlated. The procedure devised is of special value when isotope measurements are needed of structures which can be safely identified only in the fluorescence microscope, and it has been used for quantitative estimations of adrenergic innervation.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Catecholamines and m-tyramine derivatives form strongly fluorescent products on formaldehyde gas treatment according to the method of Falck and Hillarp with maximal emission at 480 and 420 mμ. respectively. Administration of the m-tyramine compounds m-tyrosine, α-methyl-m-tyrosine and 4, α-dimethyl-m-tyramine caused a depletion of the green fluorescence (max. 480 mμ) in both central and peripheral catecholamine neurons with a concomitant appearance of a blue fluorescence (max. 420 mμ) due to uptake and accumulation of the administered m-tyramine derivatives. Injection of metaraminol gave the same results in sympathetic adrenergic neurons while of the central catecholamine neurons only the dopamine nerves in the median eminence were depleted and showed uptake and accumulalation of metaraminol.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: NA depletion ; d-Amphetamine ; DSP4 ; Neonatal 6-OHDA ; Adult 6-OHDA ; Dorsal mundle 6-OHDA ; DMI ; Hyperactivity ; Rearing ; Locomotion ; Dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of neonatal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA; 1–4 doses of 100 mg/kg body weight s.c.) on the postnatal development of pyramidal neurons in several cortical regions of the rat was studied using a Golgi-Cox neuronal impregnation technique. Rats were sacrificed in the adult stage (eight weeks) and the following regions were studied: anterior frontal cortex, posterior frontal cortex (including motor cortex), anterior parietal cortex (including sensory cortex), posterior parieto-occipital cortex and cingulate cortex. Significant alterations were seen in animals which received four doses of 6-OHDA. These alterations can be summarized as follows: (1) a decreased length and branching of basolateral dendrites of pyramidal cells, with loss of dendritic spines, which were found in both the internal pyrimidal layer (layer V) and the external pyramidal layer (layer III), most abundantly in the frontal cortex and cingulate cortex; (2) an increased number of pyramidal cells of layer V with premature apical dendritic termination in layer III rather than the usual termination in layers I and II. This was most abundant in the cingulate cortex; (3) occasional disorientation of pyramidal cell apical dendrites away from the normal vertical plane by 15 or more degrees, seen in frontal, parietal and cingulate cortex; (4) an increased number of pyramidal cells with rounded somatic contours, found in frontal, anterior parietal and cingulate cortex. These phenomena were occasionally seen in normal cortex, but were significantly increased in their occurrence after four doses of 6-OHDA. Such alterations were not significant in rats treated with one or three doses of 6-OHDA. The extent and severity of morphological alterations correlate with reductions in endogenous noradrenaline (NA) in cerebral cortex, which was found to average 50% of control levels after one dose of 6-OHDA, an 80% reduction after three doses, and a 97–98% reduction after four doses, suggesting that the NA denervation must be almost complete to result in readily detectable significant morphological changes in the development of cortical pyramidal cells. No consistent changes in endogenous dopamine (DA) levels were observed, except for an increase in the cingulate cortex. The anatomical alterations in pyramidal cells described in the present study suggest that NA neurons which project into the cerebral cortex have a neurotrophic role in the postnatal development of cortex.
    Type of Medium: Electronic Resource
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