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  • 1
    Electronic Resource
    Electronic Resource
    Studies on uptake of intraventricularly administered tritiated noradrenaline and 5-hydroxytryptamine with combined fluorescence histochemical and autoradiographic techniques (1968)
    Springer
    Histochemistry and cell biology 16 (1968), S. 186-194 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Tritiated noradrenaline (NA) and 5-hydroxytryptamine (5-HT) (1.5–30 μC) have been injected intraventricularly into normal or reserpine-nialamide pretreated rats 1/2 to 2 hours before the killing. Various parts of the brains were freeze-dried, reacted with formaldehyde gas and embedded in paraffin or Araldite. Before application of the stripping film emulsion many sections were photographed in the fluorescence microscope in order to perform a combined histochemical and autoradiographic study of the monoamine neurons. By such an approach it was possible to demonstrate 1. that the accumulation of radioactivity in cell bodies after 3H-NA and 3H-5-HT injection is localized to catecholamine (CA) and 5-HT cell bodies respectively; 2. that injected 3H-NA and 3H-5-HT in the doses used relatively selectively are taken up into the NA and 5-HT nerve terminals respectively, since the distribution of grains in the sections follow that of the fluorescent terminals; 3. that the accumulation of silver grains only reaches the zone (200–400 μ) close to the ventricles and the ventral part of the subarachnoidal space. By grain counting it was possible to estimate that the degree of concentration of radioactivity in the monoamine cell bodies was up to 4 times that in the immediate surroundings. — The Araldite sections consistently gave a better resolution in the autoradiographic picture than the paraffin sections. It is postulated that freeze-drying and plastic embedding for autoradiography will be a valuable method for the cellular demonstration of certain biogenic amines which are not easily demonstrated by the histochemical fluorescence method and of other biologically active water-soluble compounds, since diffusion will be restricted to a minimum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280617
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  • 2
    Electronic Resource
    Electronic Resource
    Cerebellar monoamine nerve terminals, a new type of afferent fibers to the cortex cerebelli (1969)
    Springer
    Experimental brain research 9 (1969), S. 63-72 
    Details
    ISSN: 1432-1106
    Keywords: Noradrenaline and 5-hydroxytryptamine nerve terminals ; Cortex cerebelli ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The monoamine innervation of the cerebellum of the rat has been studied by both in vivo and in vitro techniques using the histochernical fluorescence method for the demonstration of catecholamines (CA) and certain tryptamines. By way of a pharmacological approach using inter alia protriptyline, which acts mainly by blocking the membrane pump of the noradrenaline (NA) neurons, evidence was obtained that CA nerve terminals in the cerebellum mainly represent NA nerve terminals. These were found to innervate practically all parts of the cerebellar cortex with a patchy innervation pattern and with an innervation of especially the anterior and posterior lobes. The terminals mainly seem to make axodendritic contacts in the molecular and granular layers without any strict localization of the terminal plexus to any special plane of the cerebellar folia. The fibers enter the cerebellum via the inferior cerebellar peduncle and run in the white matter of the cortex cerebelli. Incubation studies with 6-hydroxytryptamine indicate that there exists also a 5-hydroxytryptamine (5-HT) innervation of the cortex cerebelli, although not as pronounced as the NA innervation. The 5-HT nerve terminals are very fine, varicose fibers and innervate mainly the molecular layer, especially of the anterior lobe. The terminals run mainly in the transverse plane of the folium parallel to the surface. Thus, the pattern of innervation of these 5-HT afferents is different from that of the NA nerve terminals. In the uvula, structures which may represent the “rosettes” of the mossy fibers or golgi axon terminals in the granular layer take up and accumulate monoamines after incubation with amine in vitro. The exact nature of these structures remains to be elucidated.The cerebellar nuclei receive a very low to low degree of innervation of NA and 5-HT nerve terminals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235452
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  • 3
    Electronic Resource
    Electronic Resource
    Histochemical studies on the distribution of catecholamines and 5-hydroxytryptamine after intraventricular injections (1968)
    Springer
    Histochemistry and cell biology 13 (1968), S. 16-28 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Using the histochemical method for the demonstration of DA, NA and 5-HT it has been possible to demonstrate, in reserpine treated rats, that intraventricularly administered DA, NA, α-methyl-DA and α-methyl-NA in doses of 1–2 μg are specifically taken up by the parts of the DA and NA neurons lying close to the ventricles and the subarachnoidal space. The distribution of this uptake is described in detail. No uptake and accumulation of DA and NA was observed unless the monoamineoxidase had been inhibited whereas the α-methylated compounds which are resistant to monoamineoxidase accumulated without monoamineoxidase inhibition. Intraventricularly administered 5-HT was specifically taken up and accumulated in the 5-HT neurons within the same zone provided that monoamineoxidase had been inhibited. The distribution of this uptake is described in detail. After high doses of CA (5–10 μg) these amines accumulated to some extent also in the 5-HT neurons while no such accumulation was observed in the CA neurons after high doses of 5-HT. Thus, the present results indicate that there exists a specific reserpine-resistant, amine-concentrating mechanism at the nerve cell membrane of CA and 5-HT neurons. In areas where the exogenous amine concentrations probably were high there also occurred an accumulation of DA and NA in the CA neurons although the monoamineoxidase was not inhibited. Finally, in a certain area of the hypothalamus, CA was found to accumulate even after low doses (1–2 μg), in nerve cell bodies which probably normally do not contain CA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00303872
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  • 4
    Electronic Resource
    Electronic Resource
    The effect of lithium on cerebral monoamine neurons (1967)
    Springer
    Psychopharmacology 11 (1967), S. 345-353 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lithium, administered intraperitoneally to rats in doses of 2.5 to 15 meq/kg body wt., did not alter the noradrenaline content of the brain; but when given together with a tyrosine-hydroxylase inhibitor, H 44/68, it produced a depletion of brain noradrenaline which was more pronounced than that produced by H 44/68 alone. The effect of lithium on cerebral noradrenaline depletion appeared to be correlated with the lithium concentration in the brain tissue. Histochemical studies also showed that the administration of lithium and H 44/68 together led to a stronger reduction in fluorescence intensity of the noradrenaline neuron terminals in the brain than that seen after H 44/68 alone. Lithium did not affect the depletion of dopamine produced by H 44/68 or the depletion of 5-hydroxytryptamine produced by the tryptophanhydroxylase inhibitor H 22/54.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404612
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  • 5
    Electronic Resource
    Electronic Resource
    Central catecholamine neurons and conditioned avoidance behaviour (1967)
    Springer
    Psychopharmacology 11 (1967), S. 439-447 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With the help of the histochemical fluorescence method for the demonstration of dopamine, noradrenaline and 5-hydroxytryptamine and inhibitors of tyrosine-hydroxylase the activity of the central monoamine neurons has been studied in rats after performance of a negatively reinforced conditioned avoidance behaviour. Support was obtained for the view that the central CA neurons (possibly mainly NA neurons) increase their activity during performance of the present kind of conditioned avoidance behaviour. The results suggest that the noradrenaline nerve terminals to the prosencephalon play an important role as an arousal system essential for the performance of behavioural activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405029
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  • 6
    Electronic Resource
    Electronic Resource
    Some observations on the site of action of Oxypertin (1967)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 256 (1967), S. 450-463 
    Details
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The effect of oxypertin 1-[2-(5,6-dimethoxy-2-methyl-3-indolyl)ethyl]-4-phenylpiperazine on central and peripheral monoamine containing neurons of rats was investigated both histochemically (fluorescence microscopy) and biochemically: 1. Oxypertin (30–70 mg/kg) depleted the dopamine, noradrenaline, and serotonin containing neurons in the central nervous system. After administration of 70 mg/kg oxypertin the noradrenaline level of the brain was more reduced (−88%) than the dopamine (−49%) and serotonin (−46%) level. 2. The noradrenaline content of the adrenergic ground plexus of the iris and the heart was also diminished by oxypertin. In the iris the recovery of the spezific fluorescence due to noradrenaline was complete 24 hrs after the injection, whereas the noradrenaline content of the heart reached control values after 72 hrs only. 3. Pretreatment of the animals with the monoamine oxidase inhibitor nialamide prevented the depletory effect of oxypertin. 4. The accumulation of exogenous noradrenaline in central (median eminence) and peripheral catecholamine neurons (iris, heart) previously depleted on amines by inhibition of endogenous noradrenaline synthesis with α-methyl-p-tyrosine was blocked by oxypertin. 5. In vitro oxypertin (10−5 M) caused also a decrease of the fluorescence intensity in rat irides and inhibited the accumulation of noradrenaline and α-methylnoradrenaline resp. in the noradrenergic neurons previously depleted of endogenous noradrenaline by α-methyl-p-tyrosine (inhibition of tyrosine hydroxylase) and reserpine resp. 6. It is concluded that the depletory effect of oxypertin on monoamine containing neurons in vivo is mainly due to a reserpine-like blockade of the uptake storage mechanism of the amine storage granules, in vitro, however, additionally by inhibition of the reserpine-resistant uptake mechanism localized in the cell membrane.
    Notes: Zusammenfassung Histochemische (fluorescenzmikroskopische) und biochemische Untersuchungen über die Wirkung von Oxypertin 1-[2-(5,6-dimethoxy-2-methyl-3-indol)äthyl]4-phenylpiperazin auf zentrale und periphere monoaminhaltige Neurone der Ratte haben ergeben: 1. Oxypertin (30–70 mg/kg) verminderte den Dopamin-, Noradrenalin- und Serotoningehalt in den entsprechenden Neuronen des Zentralnervensystems. Das Gehirn verarmte stärker an Noradrenalin (−88%) als an Dopamin (−49%) und Serotonin (−46%). 2. Der Noradrenalingehalt der Iris und des Herzens wurde durch Oxypertin ebenfalls herabgesetzt. 24 Std nach der Injektion war die normale Fluorescenzintensität der Iris wiederhergestellt, während die Noradrenalinverarmung im Herzen (−90%) erst nach 72 Std ausgeglichen war. 3. Die Verarmung der monoaminhaltigen Neurone durch Oxypertin war nach Vorbehandlung der Versuchstiere mit dem Monoaminoxydasehemmstoff Nialamid aufgehoben. 4. Oxypertin verhinderte die Anreicherung von exogenem Noradrenalin in zentralen (Eminentia medialis) und peripheren (Iris und Herz) Brenzcatechinamin-Neuronen, nachdem diese durch Hemmung der endogenen Noradrenalinsynthese mit α-Methyl-p-tyrosin an Aminen verarmt worden waren. 5. Auch in vitro bewirkte Oxypertin (10−5 M) eine Abnahme der Fluorescenzintensität der Ratteniris und hemmte die Anreicherung von Noradrenalin bzw. α-Methylnoradrenalin in den noradrenergischen Nerven nach deren vorhergehender Verarmung an Noradrenalin durch α-Methyl-p-tyrosin bzw. Reserpin. 6. Es wird geschlossen, daß die Verarmung der monoaminhaltigen Neurone durch Oxypertin in vivo — reserpinähnlich — durch Blockierung des in der Granulamembran und in vitro durch eine Beeinträchtigung auch des in der Zellmembran lokalisierten — reserpinresistenten — Aufnahmemechanismus für Brenzcatechinamine verursacht ist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00536803
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  • 7
    Electronic Resource
    Electronic Resource
    Noradrenaline nerve terminals in the hippocampal region of the rat and the guinea pig (1967)
    Springer
    Cell & tissue research 78 (1967), S. 463-473 
    Details
    ISSN: 1432-0878
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The hippocampal region of the rat has been studied with the histochemical fluorescence method for demonstration of catecholamines and 5-hydroxytryptamine. Noradrenalin nerve terminals of characteristic appearance were observed throughout the region, but the density of the terminals in the various areas differed considerably. The highest amount of terminals were seen in the hilus of the area dentata of the rat. Otherwise, noradrenalin nerve terminals constitute a small percentage of the afferents to the hippocampal region. Noticeable differences existed between rat and guinea-pig. In both species there was a conspicuous lack of stratification and delineation of areas as compared with the pictures seen with most other methods, which have revealed precise architectonic patterns.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334281
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  • 8
    Electronic Resource
    Electronic Resource
    Evidence for the existence of monoamine neurons in the central nervous system (1965)
    Springer
    Cell & tissue research 65 (1965), S. 573-596 
    Details
    ISSN: 1432-0878
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary With the help of the highly specific and sensitive fluorescence method of Falck and Hillarp together with the histochemical and pharmacological criteria for the specificity of the fluorescence reaction convincing evidence has been obtained that the fine, varicose nerve fibres observed in a vast number of regions in the mammalian central nervous system (mouse, hamster, rat, guineapig, rabbit, cat), which exhibit a green or yellow fluorescence, contain primary catecholamines and 5-HT respectively. Strong support has been given for the view that CA fibres showing a rapid recovery after administration of α-MMT contain DA, while those showing a slow recovery contain NA. There is little doubt that the monoamine-containing fibres in the brain represent the terminal ramifications of axons belonging to specific monoamine neurons and that they are true synaptic terminals. They seem to make their contacts via the varicosities which have extremely high concentrations of amines and in all probability represent the presynaptic structures, specialized for synthesis, storage and release of the amines. The central monoamine terminals thus have the same characteristic appearance as the adrenergic synaptic terminals in the peripheral nervous system. All the data strongly support the view that the specific central neurons giving rise to the terminals are monoaminergic, i.e. function by releasing their amines from the synaptic terminals. Consequently, DA, NA and 5-HT seem to be central neurotransmitters. Not only the median eminence but also the nuc. caudatus putamen, tuberculum olfactorium, nuc. accumbens and the small circumscribed areas medial to nuc. accumbens contain very fine (partly sublightmicroscopical) CA terminals. These areas react to treatment with reserpine, nialamide-dopa and α-MMT in the same way and since the nuc. caudatus putamen and tuberculum olfactorium are known to have a high DA content it seems likely that abundant DA terminals are accumulated in these special areas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00337069
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  • 9
    Electronic Resource
    Electronic Resource
    A fluorescence and electron microscopic study on central monoamine nerve cellsThis work has been supported by research grants (12x-715-01 and W 417) from the Swedish Medical Research Council and by a grant from “Stiftelsen G. och T. Svenssons Minne.” (1966)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 155 (1966), S. 33-40 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: By combining the histochemical fluorescence method for catecholamines (CA) and 5-hydroxytryptamine (5-HT) with electron microscopy it has been possible to study the ultrastructure of the central CA and 5-HT nerve cells of the locus coeruleus and the nuc. raphe dorsalis. The CA and the 5-HT nerve cells have the same ultrastructural characteristics: a well-developed granular reticulum and a peri-nuclearly situated, prominent Golgi apparatus which almost completely surrounds the nucleus. Agranular vesicles (300-500 Å in diameter) are found mainly in a perinuclear area in association with the Golgi apparatus. They are similar to the small agranular vesicles present in large numbers in the presynaptic bags. A few complex vesicles and granular vesicles (600-1200 Å in diameter) are noticed throughout the cytoplasm. No certain changes are observed in the different types of vesicles after treatment with reserpine or MAO inhibitors.It is suggested that the agranular vesicles contain CA, since these vesicles are most numerous in a perinuclear area where the concentration of the amines are highest. In spite of the low number of agranular vesicles present as compared to the high number found in nerve terminals they might store at least a considerable part of the amines, since the amine concentrations are much lower (100-1000 X) in the nerve cells than in the terminals.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091550105
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  • 10
    Electronic Resource
    Electronic Resource
    Further evidence for the presence of nigro-neostriatal dopamine neurons in the rat (1965)
    New York, NY [u.a.] : Wiley-Blackwell
    American Journal of Anatomy 116 (1965), S. 329-333 
    Details
    ISSN: 0002-9106
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: With the help of the highly specific and sensitive histochemical fluorescence method of Falck and Hillarp for the cellular demonstration of monoamines the catecholamine-containing cell-bodies within the brain stem have been studied after unilateral removal of a large part of the neostriatum 1 to 28 days after the operation.Most of the catecholamine-containing cell-bodies within the substantia nigra  -  but no other monoamine-containing cell-bodies  -  appeared to be distinctly increased in fluorescence intensity and somewhat swollen 2 to 4 days after operation while after 3 to 4 weeks they showed a marked to very marked decrease in fluorescence intensity together with marked degenerative changes. Parallel with the changes in the cell-bodies there occurred a rapid and marked accumulation of catecholamines within very abundant swollen nerve fibers in the internal capsule. These nerve fibers were traced caudally via the retrolenticular part of the internal capsule down to the crus cerebri. These results together with those in a previous paper (Andén, Carlsson, Dahlström, Fuxe, Hillarp and Larsson, 1964) seem to provide conclusive evidence for the presence of nigro-neostriatal dopamine neurons.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aja.1001160117
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