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  • Precipitated morphine withdrawal  (3)
  • Rats  (3)
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  • 1
    Digitale Medien
    Digitale Medien
    Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats (1973)
    Springer
    Psychopharmacology 33 (1973), S. 19-38 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Development of Morphine Dependence ; Precipitated Withdrawal ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In rats implanted subcutaneously with morphine containing pellets different degrees of dependence were induced by varying the dosage, frequency of implantation and duration of exposure to morphine. Withdrawal was precipitated by intraperitoneal injection of morphine antagonists, mostly levallorphan. The absorption of morphine from the subcutaneous depots was estimated chemically. When withdrawal was precipitated with a constant dose of antagonist the frequency of occurrence of various counted signs and the presence of some checked signs were studied in respect to varying degrees of dependence. The results were compared to those obtained after administration of increasing doses of antagonist in groups of animals that had developed a constant degree of dependence. In both types of experiments the results were rather similar. Some signs became progressively more pronounced when dependence got stronger or the dose of the antagonist was increased. In contrast, other signs showed a maximal frequency at the lower degrees of dependence or after administration of the lower doses of antagonist and decreased or even disappeared when the degree of dependence was higher or the dose of antagonist further increased. Obviously, in withdrawal the intensity of “recessive” signs like writhing and wet dog shaking declines when “dominant” signs like jumping, flying (a vigorous kind of jumping) and teeth chattering increase. An inverse relationship between the occurrence of various signs could also be shown within the 30 min observation period. Changes in the integrative mechanisms controlling behaviour during withdrawal are supposed to be the reason for this shift of signs. In other experiments in which the interval between each morphine implantation was prolonged the frequency of some signs like jumping and teeth chattering tented to plateau. This finding seems to be correlated to some kind of steady state on resorption of morphine from the subcutaneous depots, as was found in chemical analysis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00428791
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  • 2
    Digitale Medien
    Digitale Medien
    Sites of action of morphine involved in the development of physical dependence in rats (1977)
    Springer
    Psychopharmacology 53 (1977), S. 33-37 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Precipitated morphine withdrawal ; Brain sites of action ; 3H-Naloxone ; Autoradiography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphine withdrawal was precipitated by injection of 3H-naloxone into restricted parts of the ventricular system of rats made tolerant to and dependent on morphine by repeated pellet implantation. The spread of the drug was evaluated by autoradiography and compared with the withdrawal signs precipitated in the same experiment. When the antagonist could spread into the tissue surrounding the 4th ventricle and the caudal parts of the aqueduct (penetration depth about 1.5 mm), a strong withdrawal syndrome was displayed. In contrast, only weak or no withdrawal signs were observed when the spread of naloxone was restricted to the surroundings of the lateral ventricles, the 3rd ventricle, and the rostromedial parts of the aqueduct. The same was true when the spread of the antagonist was limited to the ventral surface of the brain stem. It is concluded that structures located in the anterior part of the fossa Rhomboidea, and possibly also in the caudal part of the periaqueductal grey matter, are sites for the development of physical dependence on morphine giving rise to the withdrawal signs studied in these experiments.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00426691
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  • 3
    Digitale Medien
    Digitale Medien
    Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats (1974)
    Springer
    Psychopharmacology 39 (1974), S. 121-143 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Expression of Morphine Withdrawal ; Catecholaminergic Mechanisms ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of various drugs affecting catecholaminergic mechanisms on the precipitated morphine withdrawal syndrome was studied in rats which had developed a medium degree of dependence. Administration of low doses of d-amphetamine, cocaine, and L-Dopa shortly before precipitating withdrawal by levallorphan induced a dose-dependent increase of “dominant” withdrawal signs such as jumping and a decrease of “recessive” signs such as wet dog shaking; signs such as diarrhea and ptosis decreased, whereas rhinorrhea, salivation and lacrimation increased. A qualitatively very similar change in withdrawal signs occurred when withdrawal was precipitated in extremely highly dependent rats and/or increasing doses of the antagonist were administered. Therefore, the effects of the above drugs are interpreted as potentiation of withdrawal. Pretreatment with higher doses of the same drugs provoked strong stereotyped behaviour which obviously suppressed the occurrence of other motor signs. Activation of noradrenergic or dopaminergic mechanisms with desipramine or apomorphine induced an increase in the intensity of withdrawal, which was, however, much more pronounced after the former than the latter drug. When catecholamines (CA) were previously depleted by alpha-methyl-para-tyrosine (AMT), apomorphine lost a great part of its effectiveness. Blockade of CA synthesis by AMT alone resulted in decreased jumping while at the same time writhing largely increased, thus, inducing a profile of signs characteristic for a weak withdrawal. Selective inhibition of noradrenaline synthesis by FLA-63 resulted in a reduction in withdrawal intensity. Ro 4-4602 + L-Dopa, given after AMT, antagonized and reversed the reduction of withdrawal, but this effect was not so pronounced when by additional pretreatment with FLA-63 NA levels remained low. It is concluded that of both brain CA especially noradrenaline is involved in the manifestation of the morphine withdrawal syndrome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00440843
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  • 4
    Digitale Medien
    Digitale Medien
    Comparison of withdrawal precipitating properties of various morphine antagonists and partial agonists in relation to their stereospecific binding to brain homogenates (1976)
    Springer
    Psychopharmacology 46 (1976), S. 41-51 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Precipitated morphine withdrawal ; Morphine antagonists and partial agonists ; Stereospecific opiate binding ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In morphine-dependent rats the withdrawal precipitating properties of various morphine antagonists and partial agonists were studied by quantitatively evaluating a variety of different withdrawal signs. A comparison of the dose response curves of the various substances obtained for the different signs revealed marked differences in respect to the lowest effective doses (EDs) necessary to precipitate the withdrawal signs as well as in the maximum frequencies of the signs induced. The “pure” antagonist, naloxone, which was judged very potent according to the ED, precipitated the lowest levels of jumping, whereas certain partial agonists of the benzomorphane type, which were less potent according to the ED, induced very high levels of this sign. These latter compounds, however, failed to precipitate “complete” withdrawal, as evidenced by the nearly complete absence of some of the withdrawal signs. The jumping precipitating potency of the antagonists as judged from the ED was found to be highly correlated to the stereospecific binding of these substances to rat brain homogenate. On the other hand, the ability of the substances to precipitate high levels of jumping was seen to increase, at least within a certain range, with increasing degree of agonistic properties, as indicated by the ratio of stereospecific binding in the presence and absence of sodium.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00421548
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  • 5
    Digitale Medien
    Digitale Medien
    Sites of action of morphine involved in the development of physical dependence in rats (1976)
    Springer
    Psychopharmacology 46 (1976), S. 141-147 
    Details
    ISSN: 1432-2072
    Schlagwort(e): Precipitated morphine withdrawal ; Intraventricular injection ; Microinjection ; Various morphine antagonists ; Sites of action
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphine withdrawal was precipitated by injection of various morphine antagonists into restricted parts of the ventricular system or by microinjection of levallorphan into specific brain areas of rats made dependent on morphine by repeated pellet implantation. When the antagonists could spread only within the lateral ventricles and the 3rd ventricle, a weak withdrawal syndrome was induced; by antagonist administration into the restricted 4th ventricle, however, strong withdrawal signs like jumping were elicited even at small dosages. In microinjection experiments, structures in the midbrain and the lower brain stem proved to be the most sensitive to antagonist action. Although microinjections into thalamic nuclei also had some effect, it could not be excluded that the effects were due to uncontrolled spreading of the drug. This became especially clear from experiments with tritium-labeled levallorphan. It is concluded that brain structures located in the anterior parts of the floor of the 4th ventricle and/or caudal parts of the periaqueductal gray matter are important sites of action for the development of physical dependence on morphine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00421383
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