BEHAVIORAL PHARMACOLOGY OF OPIOID TOLERANCE

阿片类药物耐受性的行为药理学

• 批准号: 6240147
• 负责人: ALICE M YOUNG
• 金额: $ 2.69万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240147
• 关键词: behavioral /social science research tag; behavioral medicine; drug tolerance; endogenous opioid; fentanyl; laboratory rat; morphine; narcotic antagonists; neuropharmacology; opioid receptor; pigeons; sensory discrimination

The aims of this MBRS Associate Investigator application are to provide training in psychopharmacology, behavioral neuroscience, and receptor pharmacology for undergraduate and graduate minority students. Research support is provided by National Institute on Drug Abuse grants R01DA03796 (Behavioral pharmacology of opioid tolerance) and K02 DA00132 (Behavioral pharmacology of tolerance processes). These projects use drug discrimination assays to assess how pharmacological and behavioral factors modulate development of tolerance to discriminative effects of mu opioids, with particular attention to patterns of tolerance and cross-tolerance among opioids that differ in relative intrinsic efficacy. The goal of MBRS research training in my laboratory is to provide specialized instruction in the design, execution, and analysis of research projects in the area of opioid behavioral pharmacology. The first project in which MBRS trainees will participate examines the role of agonist efficacy in patterns of tolerance and cross-tolerance to the morphine-like discriminative stimulus effects of mu opioids. Experiments will examine tolerance to mu agonists during treatment with a several doses of morphine, tolerance to the same compounds during treatment with the low efficacy mu agonist nalbuphine, and tolerance during treatment with the high efficacy agonist fentanyl. A second project will examine the stimulus effects of opioids in opioid- dependent subjects. A third project, which will serve as the Ph.D. dissertation project for MBRS trainee Tonia Richardson, will use irreversible opioid receptor antagonists to independent test the hypothesis that differences in tolerance are related to differences in agonist intrinsic efficacy. A fourth project will study stimulus effects of low efficacy agonists per se. by establishing representative compounds as discriminative stimuli and examining patterns of generalization and cross- tolerance. A final project will examine whether up-regulation of opioid binding sites is followed by differential changes in stimulus effects of lower and higher efficacy agonists. In addition to conducting individual research projects, MBRS students will attend regular laboratory meetings and seminars in behavioral science and psychopharmacology, and will be encouraged to participate in semi-annual two-day research meetings held with members of neighboring behavioral pharmacology research laboratories and to present their results at national research meetings.

该MBRS副研究人员应用的目的是提供 心理药理学，行为神经科学和受体培训 本科和研究生少数学生的药理学。 研究 支持由美国国家药物滥用研究所R01DA03796提供 （阿片类药物耐受性的行为药理学）和K02 DA00132（行为 耐受过程的药理学）。 这些项目使用药物 歧视测定法以评估药理和行为因素如何 调节对MU阿片类药物歧视作用的耐受性的发展， 特别注意耐受性和交叉耐受模式 在相对内在功效不同的阿片类药物中。 MBR的目标 我实验室的研究培训是提供专业教学 研究项目的设计，执行和分析 阿片类型行为药理学。 MBRS受训者的第一个项目 将参与检查激动剂功效在模式中的作用 耐受性和对吗啡样判别刺激的耐受性 MU阿片类药物的作用。 实验将检查对MU激动剂的耐受性 在用几剂吗啡治疗期间，对同一的耐受性 低疗效MU激动剂Nalbuphine治疗期间的化合物， 高疗法激动剂芬太尼治疗期间的耐受性。 一个 第二个项目将检查阿片类药物在阿片类药物中的刺激作用 依赖主题。 第三个项目，将作为博士学位。 MBRS学员Tonia Richardson的论文项目将使用 不可逆的阿片类受体拮抗剂独立检验假设 公差的差异与激动剂的差异有关 内在功效。 第四个项目将研究低的刺激效应 效力激动剂本身。通过建立代表性化合物 歧视性刺激以及检查概括和跨的模式 宽容。 最终项目将检查阿片类药物的上调是否上调 结合位点之后是刺激效应的差异变化 较低和更高的效力激动剂。 除了进行个人 研究项目，MBRS学生将参加定期的实验室会议 和行为科学和心理药理学的研讨会，将是 鼓励参加半年度的为期两天的研究会议 与邻近行为药理学研究实验室的成员 并在国家研究会议上介绍他们的结果。