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  • 1
    ISSN: 1432-2072
    Keywords: Opioid ; Genetics ; Self-administration ; CXBK/ByJ ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is commonly thought thatμ-receptors play an important role in the reinforcing effects of opioids. In the present study, inbred strains widely divergent in CNS opiate receptor densities were used to investigate the influence of genetic variation in receptor concentration on opioid-reinforced behavior. In particular, the CXBK/ByJ mice were used as an investigative tool because of their significantly lower number of CNSμ opioid receptors. The behavioral pharmacology of opioids in theμ-deficient CXBK/ByJ mice was compared to other commonly used inbred mouse strains, C57BL/6J and BALB/cJ, and the opiate receptor rich CXBH/ByJ mice. Operant opioid reinforced behavior, opioid-induced locomotor stimulation, analgesia and respiratory depression were investigated in all four inbred strains. To assess the acquisition and maintenance of opioid reinforced behavior, oral self-administration of the potent benzimidazole opioid, etonitazene, was determined using an operant fixed-ratio schedule of reinforcement (FR 8). Acquisition of etonitazene-reinforced behavior was established in all four strains including theμ-deficient CXBK/ByJ mice. However, there were significant genetic differences in the amount of drug intake during the maintenance of opioid-reinforced behavior and extinction behavior following vehicle substitution. For example, drug intake was significantly greater in the BK versus BH mice during the maintenance phase and an extinction burst was seen in the BH but not the BK mice following vehicle substitution. Thus,μ-receptor density may not account for individual variability in the acquisition of opioid-reinforced behavior under these conditions. Sensitivity to etonitazene-induced respiratory depression, stimulation of locomotor activity and analgesia were unrelated to drug intake during self-administration sessions across these four inbred strains. These data indicate that inherited differences in CNSμ-opiate receptor concentrations do not affect acquisition of etonitazene-reinforced behavior.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Reinforcement ; Intravenous self-administration ; Strain differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. However, factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences and effects of pre-exposure to nicotine have not been examined. Male Sprague-Dawley or Long-Evans rats were surgically prepared with indwelling jugular catheters and 3 days later received chronic injections of nicotine (0.4 mg/kg SC) or vehicle (saline, 1 ml/kg) for 7 days in their home cage. The next day, 2-h daily test sessions were initiated, during which rats were given the opportunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio (FR-1) schedule of reinforcement with a 20-s time out after each infusion. One hole was defined as active while pokes in the other hole were recorded but had no scheduled consequence. The response requirement was increased progressively to five (FR-5) over successive sessions. Both saline- and nicotine-pretreated Sprague-Dawley rats showed a preference for the active hole, while only the saline-pretreated Long-Evans rats acquired the self-administration as defined by significant differences between responding in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed stable levels of maintained responding for nicotine, substituting saline for the nicotine or pretreating with mecamylamine (2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained. These results support previous reports that nicotine can serve as a reinforcer in rodents and demonstrate that environmental factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration.
    Type of Medium: Electronic Resource
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