MECHANISM OF CONDITIONED TOLERANCE TO MORPHINE

吗啡条件耐受机制

• 批准号: 3207588
• 负责人: CLAIRE D ADVOKAT
• 金额: $ 9.4万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3207588
• 关键词: analgesics; brain stem transection; centrally acting drug; drug administration rate /duration; drug administration routes; drug metabolism; drug tolerance; laboratory rat; microinjections; morphine; neuropharmacology; opiate alkaloid; radioimmunoassay; spinal cord

The goal of this proposal is to develop a simplified mammalian preparation with which to examine mechanisms of behavioral tolerance to opiates. The approach taken in these studies is derived from a substantial body of evidence demonstrating that tolerance to the analgesic effect of opiates is profoundly modified by the context in which the analgesic responses are assessed. Such responses include the defensive tail-withdrawal (flick), which can be elicited in both, intact rats, and in rats who have undergone a complete spinal transection. This fact provides an opportunity to examine environmental modulation of opiate tolerance in a chronic, unanesthetized spinal animal, a preparation which may subsequently be amenable to neurophysiological analysis. These experiments will therefore utilize standard nociceptive procedures (the hot plate and tail flick) to evaluate the contribution of environmental contingencies, both associative and nonassociative, to tolerance. Three preparations will be studied: a. intact, unoperated rats, b. intact rats sustaining spinal catheters for the intathecal administration of morphine and c. spinally transected rats. The extend to which behavioral tolerance can be modulated by environmental contingenices will be determined in each of these successively reduced preparations. In concert, these investigations will provide a valuable approach with which to gain insight into both, drug tolerance as well as the biological bases of learning and memory.

该提议的目的是制定简化的哺乳动物准备 借此来检查对阿片类药物的行为耐受性的机制。 这 这些研究中采取的方法是从一大堆物体中得出的 证明对阿片类药物镇痛作用的耐受性的证据是 通过镇痛反应是 评估。 这样的反应包括防御性尾巴（轻弹）， 可以在完整的老鼠和经历的老鼠中引起的 完整的脊柱横断。 这个事实提供了一个机会 检查慢性阳性的环境调制 未经麻醉的脊柱动物，这种制剂随后可能是 可以接受神经生理分析。 因此，这些实验将使用标准的伤害性程序 （热板和尾部轻弹）评估 环境突发事件，无论是联合和非社交的 宽容。 将研究三个准备工作：完整，不经过 老鼠，b。完整的老鼠，维持脊柱的脊柱导管 吗啡和c的给药。旋转的大鼠。 扩展到 可以通过环境脉络膜调节哪种行为耐受性 将在这些连续减少的准备工作中确定。 在 音乐会，这些调查将提供一种有价值的方法 为了深入了解两者，药物耐受性以及生物碱 学习和记忆。