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  • 1
    Electronic Resource
    Electronic Resource
    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
    Keywords: Expression of Morphine Withdrawal ; Catecholaminergic Mechanisms ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00440843
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    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
    Keywords: Precipitated morphine withdrawal ; Morphine antagonists and partial agonists ; Stereospecific opiate binding ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421548
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    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
    Keywords: Development of Morphine Dependence ; Precipitated Withdrawal ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428791
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    Paper (German National Licenses)
    Fulltext
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