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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Repeated experience with naloxone facilitates acute morphine withdrawal: potential role for conditioning processes in acute opioid dependence.
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Repeated experience with naloxone facilitates acute morphine withdrawal: potential role for conditioning processes in acute opioid dependence.

机译：纳洛酮的反复使用经验可促进急性吗啡戒断：在急性阿片类药物依赖中调节过程的潜在作用。

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Single injections with morphine can induce a state of acute opioid dependence in humans and animals, typically measured as precipitated withdrawal when an antagonist such as naloxone is administered 4-24 h after morphine. Repeated treatment with morphine at 24-h intervals can result in a progressive shift in potency of naloxone to produce such acute withdrawal signs, including suppression of operant responding for food reward. The current study characterized fully both morphine and naloxone dose-effect functions in an effort to establish the relative contributions of repeated morphine vs. repeated naloxone (Nal) experience to these potency shifts. Rats trained on an FR15 schedule for food received four vehicle or morphine injections (0.56-5.6 mg/kg sc), spaced 24 h apart. Four hours after each morphine pretreatment (Repeat Nal), or 4 h after the fourth and final morphine pretreatment only (Single Nal), a cumulative dose-effect function for naloxone-induced suppression of responding was determined. Vehicle-pretreated (Morphine Naive) rats showed little change in the naloxone dose effect function even after four cumulative dose-effect determinations. By contrast, a progressive increase in naloxone potency was observed following successive pretreatments with morphine under Repeat Nal conditions, and the magnitude of naloxone potency shift was morphine dose dependent. At a morphine dose of 5.6 mg/kg, repeated naloxone experience in the presence of morphine was not an absolute requirement to produce an increase in naloxone potency across days, but repeated naloxone could potentiate the magnitude of the observed shift, indicating both experience-independent and experience-dependent processes at work. At lower doses of morphine (1.0 and 3.3 mg/kg) no shift in naloxone potency was observed across days of morphine treatment in the absence of repeated naloxone experience (Single Nal conditions), indicating an increasing contribution of naloxone experience-dependent processes as dose of morphine was decreased. Itis argued that these experience-dependent processes in the progressive shift of naloxone potency observed in the current study may reflect an important role of conditioning in the early development of opioid dependence.
机译：吗啡的单次注射可在人和动物中引起急性阿片样物质依赖状态，通常以吗啡给药后4-24小时给予拮抗剂（如纳洛酮）来衡量戒断。每隔24小时用吗啡重复治疗可导致纳洛酮产生这种急性戒断症状的能力逐步转移，包括抑制操作者对食物报酬的反应。当前的研究充分描述了吗啡和纳洛酮的剂量效应功能，以试图确定重复的吗啡与重复的纳洛酮（Nal）经历对这些药效变化的相对贡献。按FR15时间表训练的大鼠进食四次媒剂或吗啡注射（0.56-5.6 mg / kg sc），间隔24小时。每次吗啡预处理后四个小时（重复Nal），或仅在第四次也是最后一次吗啡预处理后四个小时（Single Nal），确定纳洛酮诱导的反应抑制的累积剂量效应功能。媒介物预处理的大鼠（Morphine Naive）即使在四次累积剂量效应测定后，纳洛酮剂量效应功能也几乎没有变化。相比之下，在重复Nal条件下使用吗啡进行连续预处理后，观察到纳洛酮效能的逐步提高，并且纳洛酮效能变化的幅度取决于吗啡剂量。在吗啡剂量为5.6 mg / kg时，在吗啡存在下重复服用纳洛酮并不是绝对需要每天增加纳洛酮效力，但是反复使用纳洛酮可以增强观察到的转变幅度，表明两者均与经验无关和工作中依赖经验的流程。在较低剂量的吗啡（1.0和3.3 mg / kg）下，在没有重复的纳洛酮经验（单纳尔病）的情况下，整个吗啡治疗期间纳洛酮效力没有变化，表明纳洛酮经验依赖性过程作为剂量的贡献增加吗啡的减少。据认为，在本研究中观察到的这些依赖经验的过程在纳洛酮效力的逐步转变中可能反映了调节作用在阿片样物质依赖的早期发展中的重要作用。

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