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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In morphine-dependent rats, low naloxone doses have been shown to induce conditioned place aversion, which reflects the negative motivational component of opiate withdrawal. In contrast, higher naloxone doses are able to induce a ‘full’ withdrawal syndrome, including overt somatic signs. The c-fos gene is commonly used as a marker of neuronal reactivity to map the neural substrates that are recruited by various stimuli. Using in situ hybridization, we have analysed in the brain of morphine-dependent rats the effects of acute withdrawal syndrome precipitated by increasing naloxone doses on c-fos mRNA expression. Morphine dependence was induced by subcutaneous implantation of slow-release morphine pellets for 6 days and withdrawal was precipitated by increasing naloxone doses inducing the motivational (7.5 and 15 µg/kg) and somatic (30 and 120 µg/kg) components of withdrawal. Our mapping study revealed a dissociation between a set of brain structures (extended amygdala, lateral septal nucleus, basolateral amygdala and field CA1 of the hippocampus) which exhibited c-fos mRNA dose-dependent variations from the lowest naloxone doses, and many other structures (dopaminergic and noradrenergic nuclei, motor striatal areas, hypothalamic nuclei and periaqueductal grey) which were less sensitive and recruited only by the higher doses. In addition, we found opposite dose-dependent variations of c-fos gene expression within the central (increase) and the basolateral (decrease) amygdala after acute morphine withdrawal. Altogether, these results emphasize that limbic structures of the extended amygdala along with the lateral septal nucleus, the basolateral amygdala and CA1 could specifically mediate the negative motivational component of opiate withdrawal.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 746 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 537 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Hot plate ; Ethopharmacology ; Ethogram ; Morphine ; Naloxone ; Cluster analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objectives of this study were: i) to analyse the effects of morphine and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeated hot plate measures, rats were tested before and 60, 120, 180 and 240 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were tested only once 60 min after morphine or 30 min after naloxone administration, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treatment. Behaviour was videotaped and analysed by an ethogram and ethological techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reactions (walk-sniff, immobile-sniff) and noxious-evoked elements, including primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min post-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected “thermal hyperreactivity rebound effect” after 120 min (paw-licking and hindleg-withdrawal were enhanced), although changes in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedule at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repeated test schedule, but not on single exposure to the plate. Other elements were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeated and single tests paradigms are of value for testing the effects of morphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the drug. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study.
    Type of Medium: Electronic Resource
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