Quantitation of morphine tolerance induced by pellet implantation in the rat
Quantitation of morphine tolerance induced by pellet implantation in the rat
复制标题
大鼠体内颗粒植入诱导的吗啡耐受性的定量
DOI：
10.1111/j.2042-7158.1978.tb13183.x
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发表时间：
1978
影响因子：
3.3
通讯作者：
H. Bhargava
中科院分区：
文献类型：
--
作者：
H. Bhargava
在 3 天的时间内植入 2 个颗粒，每个颗粒含有 75 mg 吗啡碱（附表 1），在 3 天的时间内植入 4 个颗粒（附表 2），在 3 天的时间内植入 6 个颗粒（附表 3），在 7 天的时间内植入 6 个颗粒（附表 4），在 1 天的时间内植入 10 个颗粒（附表 5）。通过测定硫酸吗啡的中位镇痛剂量（AD50）来定量每个方案中大鼠的吗啡耐受程度。方案5大鼠的AD50值从3.6增加到53.1mg kg-l（15倍耐受性），而方案1大鼠仅产生三倍耐受性。方案 2 至 4 中的大鼠对吗啡的耐受性分别是 6 倍、8 倍和 13 倍。与对吗啡耐受性较高的大鼠相比，对吗啡耐受性较差的大鼠在颗粒去除时脑部和血浆中吗啡浓度较低，并且吗啡从脑部和血浆中消失得更快。数据表明，植入两个吗啡小丸会产生较低程度的耐受性，当基于大鼠或小鼠的发现与使用四个或更少数量的吗啡小丸诱导耐受时的生化数据进行比较时，应谨慎行事。吗啡颗粒植入已被用来诱导小鼠（Way, Loh & Shen, 1969; Hui & Roberts, 1975）和大鼠（Blasig, Herz & other, 1973; Cicero & Meyer, 1973; Wei, Loh & Way, 1973）对吗啡的耐受性和身体依赖性。小鼠对吗啡的耐受程度和身体依赖性已得到定量（Way 等，1969）。但大多数研究人员在大鼠中植入一或两个小丸，每个小丸含有 75 毫克吗啡碱，为期 3 天，并假设已形成足够程度的耐受性和身体依赖性。然而，植入 hvo 吗啡丸三天后，大鼠的耐受性仅达到 2 至 3 倍（Bhargava、Afifi 和 Way，1973）。 10 个丸剂，每个丸剂含有 75 mg 吗啡碱，超过 10 天产生高度依赖性，而 4 个丸剂超过 3 天产生轻度依赖性（Bhargava，1977）。当使用不同的方法诱导吗啡耐受和依赖时，得出了明显不同或矛盾的结论。例如，Shen, Loh & Way (1970) 表明
Fwo pellets, each containing 75 mg of morphine base, were implanted over a 3-day period (schedule l), four pellets over a 3-day period (schedule 2), six pellets over a 3-day period (schedule 3), six pellets over a 7-day period (schedule 4), and 10 pellets over a 1&day period (schedule 5). The degree of morphine tolerance was quantitated in rats from each schedule by determining the median analgesic dose (AD50) of morphine sulphate. The AD50 values increased from 3.6 to 53.1 mg kg-l in schedule 5 rats (a 15-fold tolerance), whereas, only a three fold tolerance was pduced in schedule 1 rats. Rats in schedules 2 to 4, developed six, eight and 13-fold tolerance to morphine, respectively. Rats that were less tolerant to morphine bd lower brain and plasma concentrations of morphine the time of pellet removal and also faster disappear-ance of morphine from brain and plasma compared with rats that were more tolerant to morphine. The data suggest that implantation of two morphine pellets produces a low degree of tolerance and that caution should be exercised when comparisons are based on findings from rats or mice the biochemical data when four or less number of morphine pellets are used to induce tolerance. Morphine pellet implantation has been used to induce tolerance to, and physical dependence, on morphine in mice (Way, Loh & Shen, 1969; Hui & Roberts, 1975) and in rats (Blasig, Herz & others, 1973; Cicero & Meyer, 1973; Wei, Loh & Way, 1973). The degree of tolerance to, and physical dependence on morphine has been quantitated in mice (Way & others, 1969). But in rats most investigators have implanted one or two pellets, each containing 75 mg Of morphine base, for a 3-day period and assumed that a sufficient degree of tolerance and physical dependence developed. However only a two to three fold tolerance in rats resulted from implantation of hvo morphine pellets for three days (Bhargava, Afifi & Way, 1973).Ten pellets, each containing 75 mg morphine base, Over 10 days produced a high degree of dependence, Whereas four pellets over 3 days produced a mild degree of dependence (Bhargava, 1977). Markedly different or contradictory conclusions have been reached when different methods were used to induce morphine tolerance and dependence. For example, Shen, Loh & Way (1970) showed that