Blockage of narcotic-induced dopamine receptor supersensitivity by cyclo(Leu-Gly).
Blockage of narcotic-induced dopamine receptor supersensitivity by cyclo(Leu-Gly).
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环（Leu-Gly）阻断麻醉诱导的多巴胺受体超敏性。
DOI：
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发表时间：
1979
影响因子：
11.1
通讯作者：
Louis B. FLEXNERf
中科院分区：
文献类型：
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作者：
R. Ritzmann;R. Walter;Hemendra N. BHARGAVAt;Louis B. FLEXNERf
我们之前曾报道过，在吗啡化之前给小鼠注射cyclo（Leu-Gly）会阻断对吗啡镇痛作用的耐受性发展以及一些身体依赖迹象的发展。在本系列实验中，我们确定了相同肽治疗对慢性吗啡治疗引起的多巴胺受体敏感性变化的影响。多巴胺受体敏感性的变化是通过测量(i)多巴胺激动剂阿波啡对运动活动的影响和（ii）对另一种多巴胺激动剂匹利贝地尔的低温反应来确定的。研究发现，接受慢性吗啡治疗的小鼠对阿波啡的需求明显减少，从而产生运动活动的增加，而且它们对匹瑞贝地尔的低温反应明显高于未接受吗啡治疗的小鼠。在吗啡治疗前2小时，每只小鼠注射0.2 μ mol的环丙酸（Leu-Gly），可防止对两种多巴胺激动剂的反应增加。在耐受性和依赖性已经形成后再给药，并没有改变吗啡耐受性和依赖性状态，也没有增强对阿波啡或匹瑞贝地尔的反应。提示多巴胺受体超敏反应可能参与了麻醉耐受和身体依赖的发生。
We have previously reported that the administration of cyclo(Leu-Gly) to mice prior to morphinization blocked the development of tolerance to the analgesic effects of morphine as well as the development of some signs of physical dependence. In the present series of experiments, the effect of the same peptide treatment on changes in dopamine receptor sensitivity induced by chronic morphine treatment were determined. Changes in dopamine receptor sensitivity were determined by measuring (i) the effect of the dopamine agonist apomorphine on locomotor activity and (ii) the hypothermic response to another dopamine agonist, piribedil. Mice that had received the chronic morphine treatment were found to require significantly less apomorphine to produce an increase in locomotor activity, and they exhibited a significantly greater hypothermic response to piribedil than did morphine-naive mice. The injection of 0.2 mumol of cyclo(Leu-Gly) per mouse 2 hr prio to morphine treatment prevented this increased response to both dopamine agonists. Administration of the peptide after the tolerance and dependence had developed did not alter morphine tolerant and dependent states states or the enhanced response to apomorphine or piribedil. It is concluded that dopamine receptor supersensitivity may be involved in the development of narcotic tolerance and physical dependence.