OPIOID OPERANT SELF-ADMINISTRATION, ANALGESIA, STIMULATION AND RESPIRATORY DEPRESSION IN MU-DEFICIENT MICE
OPIOID OPERANT SELF-ADMINISTRATION, ANALGESIA, STIMULATION AND RESPIRATORY DEPRESSION IN MU-DEFICIENT MICE
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DOI：
10.1007/bf02245094
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发表时间：
1995-01-01
影响因子：
3.4
通讯作者：
GEORGE, FR
中科院分区：
文献类型：
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作者：
ELMER, GI;PIEPER, JO;GEORGE, FR
通常认为μ受体在阿片类药物的强化作用中起重要作用。在本研究中，近交系广泛分歧的中枢神经系统阿片受体密度被用来调查阿片类药物强化行为的受体浓度的遗传变异的影响。特别是，CXBK/ByJ小鼠被用作研究工具，因为它们的CNS μ阿片受体数量显著较低。将μ缺陷CXBK/ByJ小鼠中阿片样物质的行为药理学与其他常用的近交系小鼠品系C57 BL/6 J和BALB/cJ以及阿片样物质受体丰富的CXBH/ByJ小鼠进行比较。在所有四个近交系中研究了操作性阿片样物质强化行为、阿片样物质诱导的运动刺激、镇痛和呼吸抑制。为了评估阿片类药物强化行为的获得和维持，使用操作性固定比例强化方案（FR 8）确定了强效苯并咪唑阿片类药物依托硝唑的口服自我给药。在包括mu缺陷型CXBK/ByJ小鼠在内的所有四种品系中建立了依托硝唑强化行为的获得。然而，在维持阿片类强化行为和媒介物替代后的消退行为期间，药物摄入量存在显著的遗传差异。例如，在维持阶段，BK小鼠的药物摄入量显著高于BH小鼠，并且在溶媒替代后，在BH小鼠中观察到消退爆发，但在BK小鼠中未观察到。因此，μ受体密度可能无法解释在这些条件下获得阿片类药物强化行为的个体差异。在这四个近交系中，对依托硝唑诱导的呼吸抑制、自发活动刺激和镇痛的敏感性与自我给药期间的药物摄入无关。这些数据表明，中枢神经系统μ阿片受体浓度的遗传差异不影响获得依托尼他嗪加强的行为。
It is commonly thought that mu-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 CNS mu opioid receptors. The behavioral pharmacology of opioids in the mu-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 the mu-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, mu-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 CNS mu-opiate receptor concentrations do not affect acquisition of etonitazene-reinforced behavior.