OPIATE TOLERANCE--ASSOCIATIVE & NONASSOCIATIVE EFFECTS

阿片类药物耐受性——相关性

• 批准号: 3209058
• 负责人: STEPHEN T TIFFANY
• 金额: $ 8.9万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3209058
• 关键词: association learning; behavioral habituation /sensitization; cues; drug administration rate /duration; drug tolerance; laboratory rat; morphine; narcotics; stimulus interval

The general objectives of the proposed research are to compare the tolerance that develops to the analgesic effects of morphine when drug administration is paired reliably with distinctive cues ("associative tolerance") to the tolerance that develops when drug administration is systematically unpaired with such cues ("nonassociative tolerance"). The studies in this proposal will evaluate factors controlling the development of associative and nonassociative forms of morphine tolerance, examine potential interactions between these two forms of morphine tolerance, examine potential interactions between these two forms of tolerance, explore the extent to which certain features of nonassociative tolerance can also be demonstrated in associative tolerance to morphine's analgesic effects. Furthermore, these studies will test predictions of the habituation model of drug tolerance that hypothesize that associative forms of tolerance will be retained for administration procedures promoting the development of nonassociative tolerance will disrupt the formation of associative tolerance. The studies are designed specifically to: (1) determine the magnitude of tolerance that develops when high doses of short or long interdose interval; (2) investigate the retention of morphine tolerance intervals; (3) examine the time course of the development of associative tolerance to a moderate dose of morphine; (4) determine whether a low dose of morphine can acquire and (5) determine whether behaviorally manifest compensatory responses subserve associative tolerance to morphine's analgesic effects. The results of these studies may have direct implications for the development of drug tolerance and dependence in drug abusers. The data will also have relevance for the application of various theories of drug conditioning to the clinical use of opiates, particularly with regard to the conditions that may facilitate or retard the development of tolerance. Finally, the results of these studies will provide an evaluation of hypothetical processes subserving associative tolerance that have been posited to be functional in the development and maintenance of addictive behavior.

拟议研究的一般目标是比较 耐受性会发展到吗啡时形成的镇痛作用 药物管理可靠地与独特的提示配对 （“联想公差”）对药物时产生的公差 这样的提示是系统地不配对的 （“非社交公差”）。 该提议中的研究将 评估控制联想发展的因素 吗啡耐受性的非缔合形式，检查潜力 这两种形式的吗啡耐受性之间的相互作用，检查 这两种形式的宽容之间的潜在相互作用， 探索非社交的某些特征的程度 公差也可以在联想容忍度中证明 吗啡的镇痛作用。 此外，这些研究将测试 预测药物耐受性的习惯模型 假设将保留宽容的联想形式 用于促进发展的管理程序 非社交公差会破坏联想的形成 宽容。 这些研究专门设计为：（1） 确定高剂量时出现的公差的大小 短或长的间隔； （2）调查保留率 吗啡耐受间隔； （3）检查时间课程 与中等剂量的联想耐受性发展 吗啡; （4）确定低剂量的吗啡是否可以获取 （5）确定行为上是否表现出补偿性 响应能够对吗啡镇痛作用的缔合耐受性 效果。 这些研究的结果可能对 药物耐受性和滥用药物的依赖性的发展。 这 数据还将与各种应用有关 药物调节的理论用于阿片类药物的临床使用， 特别是关于可能有助于或 延迟宽容的发展。 最后，这些结果 研究将对假设过程进行评估 被认为是的稳定的关联公差 在成瘾性的发展和维护中发挥作用 行为。