MORPHINE-TOLERANCE - IS THERE EVIDENCE FOR A CONDITIONING MODEL
MORPHINE-TOLERANCE - IS THERE EVIDENCE FOR A CONDITIONING MODEL
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DOI：
10.1126/science.635595
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发表时间：
1978-01-01
期刊：
影响因子：
56.9
通讯作者：
MAYER, DJ
中科院分区：
文献类型：
--
作者：
HAYES, RL;MAYER, DJ
西格尔报告说，暴露于预喷剂的巴甫洛夫性啡间给药可以解释对用于评估小剂量吗啡镇痛效果的测试程序的耐受性。也就是说，当大鼠吗啡(1)。他指出，动物在一个新的环境中反复暴露于吗啡，以确定它们是否对一个环境产生了相对性和测试性的不耐受，它们也被测试出对吗啡的镇痛装置的镇痛反应更少，当它们没有之前的经验时，这些相同的线索比在另一个环境中测试时更少，从而也阻止了任何不同线索的出现。因此，行为耐受性的条件对测试包括刺激的存在重新情境。同样地，当大鼠在同样的环境中接受全身吗啡治疗（给药对发展至关重要）时，为了确定它们是否相对于吗啡，它们事先接受了对止痛作用的耐受性药物治疗。我们认为西格尔的前耐受性较强，他们也进行了实验测试，尚无定论。止痛装置西格尔没有充分区分他们之前的经验。这种巴甫洛夫偶然性和持续性之间的过程最大化了观察到可能独立的行为容忍过程的机会。因此，行为宽容。充分证明凝胶的实验设计并没有区分镇痛差异之间的行为容忍现象，“不能归因于一般板的变化”测试（24）广泛研究了这一现象，指的是环境线索或存在或强大的相互作用可能发生在缺乏先前的测试经验，给药和测试设备之间（即行为容忍）。用于评估药物效果的情况。因此，先前的实验经验表明，对吗啡的镇痛作用的耐受性是一个重要的决定因素，在一定的测试中，通过爪压和药物方案产生的耐受性可以反复产生吗啡。例如，动物重新测痛以及用热板反复注射吗啡。为了支持镇痛诱导的作用，在等量吗啡的发展中，巴甫洛夫偶然性比注射动物的行为耐受性的发展提供了支持，在热板上只进行了一次测试，应该显示注射方案的可识别条件结束。刺激有助于减少肛门-西格尔认为，他的工作已经扩展了gesia，这是由于他之前的研究结果的重复配对，“通过证明吗啡的使用，耐受性的表现是特定于测试情况的。”例如，药物的环境表明，在相同的动物中，反复给药，在热板上进行吗啡测试，现在耐受的老鼠，当评估麻醉品在反复给药的环境中产生的一种环境线索的影响时，而不是在它们成为刺激物的环境中，即条件刺激或错误，有证据表明，相对不耐受（CS）（+）会导致更大的减量反应”(1)。然而，在那个实验中，他在吗啡镇痛比现在没有区分暴露于不同的环境线索的环境线索更多地与反复给药相关
Siegel reports that a Pavlovian inter-phine administration from exposure to pretation can account for tolerance to the test procedures used to evaluate the analgesia produced by small doses of morphine analgesia. That is, when rats morphine (1). He shows that animals re-were tested in a novel environment to peatedly exposed to morphine paired determinewhethertheybecamerelativewith one environment and testsituation ly nontolerant, they were also tested show less of an analgesic response to with the analgesiometric device with morphine when tested in the presence of which they had no prior experience, those same cues than when tested in the thereby also preventing any manifestapresence ofdifferent cues. Thus, he con-tion of behavioral tolerance to the test cludes that the presence of stimuli re-situation. Similarly, when rats were test~ liably associated with systemic morphine ed in the same environment in which administration is crucial to the develop-they had previously received the drug in ment of tolerance to the analgesic effects order to determine if they were relatively of morphine. We believe that Siegel's ex-more tolerant, they were also tested with periments are inconclusive. the analgesiometric device with which Siegel did not distinguish adequately they had prior experience. This procebetween Pavlovian contingencies and dure maximized the chances of observthe possibly independent process of be-ing behavioral tolerance. Therefore, Siehavioral tolerance. The well-docu-gel's experimental design did not distinmented phenomenon ofbehavioral toler-guish between differences in analgesia ance, extensively studied by the" hot attributable either to changes in general plate" test (24), refers to the fact that environmental cues or to the presence or powetful interactions can occur between absence of prior experience with the test the administration of drugs and the test apparatus (that is, behavioral tolerance). situations used to evaluate drug effects. The experiment shows only that behav-Thus, prior experience in the test appa-ioral tolerance to the analgesic effect ratus is a significant determinant of the of morphine can develop after repeatamount oftolerance produced by certain ed testing with the paw pressure andrug regimens. For example, animals re-algesiometer as well as with the hot peatedly injected with morphine and plate. tested on the hot plate show a greater re- In order to provide support for the role duction in analgesia than animals inject-of Pavlovian contingencies in the develedwithequivalentdosesofmorphinebut opment of behavioral tolerance, one tested only once on the hot plate at the should show that identifiable conditioned end of the injection regimen. stimuli contribute to the reduced anal-Siegel argues that his work has extend-gesia resulting from repeated pairings of ed previous findings" by demonstrating morphine administration with the same that the display of tolerance is specific to test situation. One should, for example, the environment in which the drug has show that, in the same animals repeatbeen administered, and that'morphine edly tested on the hot plate, the presentolerant'rats, when assessed for the ef-tation ofone environmental cue associatfects of the narcotic in an environment ed with repeated morphine administraother than that in which they became tol-tions [that is, a conditioned stimulus or erant, evidence a relatively nontolerant (CS)(+)] results in a greater decrement response"(1). Yet, in that experiment he in morphine analgesia than the presentadid not distinguish exposure to the envi-tion of a different environmental cue asronmental cues associated with mor-sociatedwithrepeatedsalineadministra-