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  • 1
    ISSN: 0022-4073
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Clonidine is used as a treatment for heroin addiction. Previous studies have reported that clonidine attenuated conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal by acting on α2 adrenoceptors (α2R). However, clonidine acts as a partial agonist both at α2R and at imidazoline-1 receptors (I1Rs). The current study was designed to determine the role of I1R in the induction of naloxone-induced CPA in morphine-dependent rats. Morphine dependence was induced by subcutaneous implantation of morphine pellets. Morphine-dependent rats were tested in a three-chamber place-aversion apparatus. A range of agonists were chosen on the basis of their differential selectivity for α2R and I1R. As expected, pretreatment with clonidine prevented naloxone-induced CPA. By contrast, pretreatment with a selective α2R agonist (UK14304) failed to prevent the CPA. We then tested whether the high affinity of clonidine for I1R was responsible for the difference between these two α2R agonists. Rilmenidine (a mixed α2R/I1R agonist) attenuated aversion to opiate withdrawal in a dose-dependent manner. The action of clonidine on I1R was studied by co-administering clonidine with RX821002, a specific α2R antagonist. Co-treatment with RX821002 and clonidine blocked naloxone-induced CPA. These results indicate that the pharmacologically protective effects of clonidine on naloxone-induced CPA are related to actions on I1RS as well as α2Rs.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 149 (2000), S. 115-120 
    ISSN: 1432-2072
    Keywords: Key words Opiate ; Withdrawal ; Place aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
    Type of Medium: Electronic Resource
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