TOLERANCE AND CROSS TOLERANCE TO THE EFFECTS OF OPIOIDS

拟议的一系列实验旨在检验这些变量 影响阿片类药物耐受性和交叉耐受性的发展 在Mu受体上具有不同程度的内在功效。在这两个地方 实验，耐受性将通过每天给药诱导 混合作用阿片类药物布托啡诺对大鼠在FR 20下的反应 食物展示时间表。在实验一中，一组大鼠将被 低剂量(3.0毫克/公斤/天)或高剂量(30毫克/公斤/天) 维持剂量布托啡诺检查耐受性的大小 发育受耐受剂维持量的影响。在……里面 实验二，给大鼠注射布托啡诺(0.3 毫克/公斤/天)在实验期之前或之后紧接着 确定服药时间与服药时间之间的时间关系 管理和行为测试在多大程度上影响 耐受性和交叉耐受性得到发展。这些研究的结果将 洞察耐受性发展为 阿片类药物，并可能确定一些程序性和药理学的 相互作用以产生不同交叉度的变量 阿片类药物的耐受性

The proposed series of experiments was designed to examine the variables influencing the development of tolerance and cross tolerance to opioids with varying degrees of intrinsic efficacy at the mu receptor. In both experiments, tolerance will be induced by daily administration of the mixed-action opioid butorphanol to rats responding under an FR 20 schedule of food presentation. In experiment I, groups of rats will be administered either a low (3.0 mg/kg/day) or high (30 mg/kg/day) maintenance dose of butorphanol to examine if the magnitude of tolerance development is influenced by the maintenance dose of the toleragen. In experiment II, rats will be administered a dose of butorphanol (0.3 mg/kg/day) either before or immediately after the experimental session to determine if the temporal relationship between the time of drug administration and behavioral testing influences the degree to which tolerance and cross tolerance develop. The results of these studies will provide insight into the mechanisms by which tolerance develops to opioids and may identify some of the procedural and pharmacological variables which interact to produce differential degrees of cross tolerance among opioids