Strain Differences in Response to Opioids

对阿片类药物反应的菌株差异

• 批准号: 6625905
• 负责人: Galen R Wenger
• 金额: $ 14.51万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625905
• 关键词: behavior test; behavioral /social science research tag; drug abuse; drug addiction; drug tolerance; endogenous opioid; genetic strain; laboratory mouse; operant conditionings; opioid receptor; pharmacology; reinforcer

DESCRIPTION (provided by applicant): Recent advances in genomics have brought to the forefront the fact that the mouse has been drastically underutilized in the behavioral aspects of drug abuse research. The use of operant schedules of reinforcement has played a significant role in our understanding of drugs of abuse and the addictive process in both humans and laboratory species. However, until recently there have been only a small number of laboratories that have attempted to utilize the mouse in experiments involving operant schedules of reinforcement. Many years of research on the genetics of the mouse has supplied the scientific community with a tremendous number of inbred strains. Many of these strains have well defined genetic differences that result in significant differences in drug effects. For example, it has been shown that marked differences exist between C57Bl/6 and DBA/2 mice in response to many effects of morphine including analgesia, locomotor activity, hypothermia, Straub-tail, and voluntary oral morphine consumption. Similarly, although tolerance to the analgesic and locomotor response to morphine has been observed to be about equal in C57Bl/6 and DBA/2 mice, tolerance to the analgesic effects of morphine has been reported not to occur following chronic administration in 129 mice. Whether strain differences exist in the stimulus or reinforcing properties as measured by drug discrimination or IV self-administration procedures in response to opioid drugs in these strains is not known. Knowledge of such differences may provide significant insight into the role of genetic differences in opioid addiction and the mechanisms of drug action. The present study will use three inbred strains of mice (C57Bl/6J, DBA/2J and 129P3/J). The study will examine the ability of receptor subtype specific opioid agonists to function as discriminative stimuli, the degree to which the drug stimulus generalizes to agonists specific for other receptor subtypes, and the ability of antagonists to block the stimulus properties. Hopefully, by utilizing these well-defined strains, it will be possible to use the known differences in genetics to provide new insight into the abuse of opioids.

描述（由申请人提供）：基因组学的最新进展带来了 最重要的是，鼠标在实际应用中的利用率极低。 药物滥用研究的行为方面。操作时间表的使用 强化在我们对药物的理解中发挥了重要作用 人类和实验室物种的滥用和成瘾过程。然而， 直到最近，只有少数实验室进行了 试图在涉及操作时间表的实验中使用鼠标 加强。多年对小鼠遗传学的研究提供了 科学界拥有大量近交系。许多 这些菌株具有明确的遗传差异，导致显着 药物作用的差异。例如，已经表明，标记为 C57Bl/6 和 DBA/2 小鼠对多种效应的反应存在差异 吗啡，包括镇痛、运动活动、低温、Straub-tail 和 自愿口服吗啡消耗量。同样，虽然容忍 据观察，吗啡的镇痛和运动反应约为 C57Bl/6 和 DBA/2 小鼠对吗啡镇痛作用的耐受性相同 据报道，129 只小鼠长期给药后不会发生这种情况。 刺激或增强特性中是否存在应变差异 通过药物歧视或静脉注射自我给药程序进行测量 这些菌株对阿片类药物的反应尚不清楚。此类知识 差异可能有助于深入了解遗传的作用 阿片类药物成瘾和药物作用机制的差异。现在的 研究将使用三种近交系小鼠（C57Bl/6J、DBA/2J 和 129P3/J）。这 研究将检查受体亚型特异性阿片类激动剂的能力 作为辨别刺激的功能，药物刺激的程度 推广到其他受体亚型特异的激动剂，并且能力 拮抗剂来阻断刺激特性。希望通过利用这些 明确的菌株，将有可能利用已知的差异 遗传学为阿片类药物滥用提供新的见解。