Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats
Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats
复制标题
大鼠对吗啡的身体依赖性在时间和剂量方面的发展以及快速戒断综合征的量化
DOI：
10.1007/bf00428791
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发表时间：
1973
期刊：
影响因子：
--
通讯作者：
S. ZieglgÄnsberger
中科院分区：
文献类型：
--
作者：
J. Bläsig;A. Herz;K. Reinhold;S. ZieglgÄnsberger
在皮下植入含吗啡颗粒的大鼠中，通过改变吗啡的剂量、植入频率和暴露时间，可以诱导不同程度的依赖。戒断是由腹腔注射吗啡拮抗剂引起的，主要是左旋吗啡。用化学方法估计吗啡在皮下的吸收，用恒定剂量的拮抗剂催促戒断时，研究不同依赖程度下各种计数体征的出现频率和某些检查体征的出现情况。这些结果与在依赖程度恒定的动物组中增加剂量的拮抗剂后获得的结果进行了比较。在两种类型的实验中，结果非常相似。当依赖性变得更强或拮抗剂的剂量增加时，一些迹象变得越来越明显。相反，其他体征在依赖程度较低或给予较低剂量拮抗剂后出现频率最高，当依赖程度较高或拮抗剂剂量进一步增加时，出现频率减少甚至消失。显然，在退缩时，扭动和湿狗抖动等“隐性”体征的强度会下降，而跳跃、飞翔(一种剧烈的跳跃)和牙齿颤动等“显性”体征的强度会增加。在30分钟的观察期内，各种体征的出现之间也可以显示出相反的关系。戒断过程中控制行为的综合机制的变化被认为是这种体征变化的原因。在其他实验中，每次注射吗啡的间隔时间延长，一些体征，如跳跃和牙齿颤抖的频率趋于平台期。这一发现似乎与化学分析中发现的皮下仓库中吗啡吸收的某种稳定状态有关。
In rats implanted subcutaneously with morphine containing pellets different degrees of dependence were induced by varying the dosage, frequency of implantation and duration of exposure to morphine. Withdrawal was precipitated by intraperitoneal injection of morphine antagonists, mostly levallorphan. The absorption of morphine from the subcutaneous depots was estimated chemically.When withdrawal was precipitated with a constant dose of antagonist the frequency of occurrence of various counted signs and the presence of some checked signs were studied in respect to varying degrees of dependence. The results were compared to those obtained after administration of increasing doses of antagonist in groups of animals that had developed a constant degree of dependence.In both types of experiments the results were rather similar. Some signs became progressively more pronounced when dependence got stronger or the dose of the antagonist was increased. In contrast, other signs showed a maximal frequency at the lower degrees of dependence or after administration of the lower doses of antagonist and decreased or even disappeared when the degree of dependence was higher or the dose of antagonist further increased. Obviously, in withdrawal the intensity of “recessive” signs like writhing and wet dog shaking declines when “dominant” signs like jumping, flying (a vigorous kind of jumping) and teeth chattering increase. An inverse relationship between the occurrence of various signs could also be shown within the 30 min observation period. Changes in the integrative mechanisms controlling behaviour during withdrawal are supposed to be the reason for this shift of signs.In other experiments in which the interval between each morphine implantation was prolonged the frequency of some signs like jumping and teeth chattering tented to plateau. This finding seems to be correlated to some kind of steady state on resorption of morphine from the subcutaneous depots, as was found in chemical analysis.