OPIOID ANALGESICS: PHARMACOLOGICAL & BEHAVIORAL FACTORS

药物化学的研究工作已经产生了阿片类药物， 非阿片类镇痛药，可有效缓解疼痛， 降低依赖潜力。 我们的目标是研究 这些化合物的镇痛作用， 对假定在μ或κ阿片类药物活性的激动剂 受体类型 镇痛活性将用2 程序，松鼠猴休克滴定程序和 新开发的大鼠热辨别程序。 在 此外，还将进行研究， 伤害性刺激（电击或热）被操纵以便 确定1）mu或kappa的影响程度 激动剂依赖于刺激强度和2）是否镇痛 在较低的温度下，对于较低效的化合物， 刺激强度 为作比较，我们亦会研究 几种μ和κ阿片激动剂对时间表的影响- 控制行为。 这些调查将在 松鼠猴、老鼠和鸽子， 物种之间的影响可以进行研究。 此外该 μ和κ阿片激动剂的辨别性刺激特性 将在老鼠和鸽子身上进行研究。 在所有这些研究中， 重点将放在与 阿片激动剂的行为效应及其介导 通过不同的阿片受体类型的影响。 为了画 这种关系，阿片激动剂将单独检查， 与阿片类拮抗剂联合使用，并在动物中耐受 到μ或κ激动剂。 然后将对 1）不同的行为特征和效力关系的基础 在阿片激动剂中，2）阿片拮抗剂在 减弱这些激动剂的作用，和3） 它们之间的交叉耐受性。

Research efforts in medicinal chemistry have produced opioid and nonopioid analgesics which may provide effective pain relief with reduced dependence potential. It is our objective to examine the analgesic effects of a number of these compounds with emphasis on agonists presumed to have activity at mu or kappa opioid receptor types. Analgesic activity will be assessed with 2 procedures, the squirrel monkey shock titration procedure and a newly developed thermal discrimination procedure in rats. In addition, studies will be carried out in which the intensity of the nociceptive stimulus (shock or heat) is manipulated in order to determine 1) the extent to which the effects of mu or kappa agonists depend on stimulus intensity and 2) whether analgesic effects might be revealed for less efficacious compounds at lower stimulus intensities. For comparison, we will also examine the effects of several mu and kappa opioid agonists on schedule- controlled behavior. These investigations will be carried out in squirrel monkeys, rats and pigeons so that differences in drug effects between species can be examined. In addition, the discriminative stimulus properties of mu and kappa opioid agonists will be investigated in rats and pigeons. In all of these studies, emphasis will be placed on the relationship between the behavioral effects of opioid agonists and the mediation of their effects through different opioid receptor types. In order to draw such relationships, opioid agonists will be examined alone, in combination with opioid antagonists and in animals made tolerant to mu or kappa agonists. Comparisons will then be made on the basis of 1) differing behavioral profiles and potency relationships among the opioid agonists 2) the potency of opioid antagonists in attenuating the effects of these agonists and 3) the occurrence of cross tolerance among them.