PENTOBARBITAL ACTIVATION IN SELECTED MOUSE LINES

所选小鼠品系中戊巴比妥的激活

• 批准号: 3214019
• 负责人: CARLTON K ERICKSON
• 金额: $ 16.18万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-05 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3214019
• 关键词: animal breeding; behavior test; behavioral medicine; brain metabolism; chordate locomotion; dopamine; dosage; drug abuse; drug adverse effect; drug tolerance; endorphins; genetic models; hypothermia; laboratory mouse; model design /development; neurochemistry; pentobarbital; pharmacokinetics; sleep

This project is designed to develop outbred lines of mice which are differentially sensitive to low doses of pentobarbital in a circular locomotor activity apparatus. The lines, designated Pentobarbital Sensitive (PBS) and Pentobarbital Insensitive (PBI), along with a control line (PBC), will be developed at The University of Texas at Austin for the purpose of discerning behavioral correlates and neurochemical mechanisms of low-dose barbiturate intoxication. Pentobarbital is the prototype barbiturate for this project based upon extensive pilot tests already completed. This five-year study will encompass a "breeding" specific aim in which mice are tested for locomotor activity in response to pentobarbital, then selected and outbred through at least 14 selection generations. At various stages of the breeding and selection process, the lines will be "characterized" (the second specific aim) for their differential responses to higher doses of pentobarbital. Parameters to be measured in these lines will be sleeptime (loss of righting reflex), hypothermia, and tolerance to sleeptime. In the third specific aim, a search for "mechanisms" of the differential responses to pentobarbital among the lines will be undertaken, through studies of pentobarbital clearance; responses to ethanol, other hypnotics, a benzodiazepine, an opiate antagonist, and an amphetamine; and brain region levels and turnover of dopamine, and brain region synthesis and concentrations of opiopeptides. The hypothesis is that these lines will be useful for studying the specific neurochemical changes related to the intoxication seen when low doses of a barbiturate are given. The proposed studies will provide information on the mechanisms behind barbiturate's intoxicating effects in mice after low doses, and perhaps in man after abusable doses of pentobarbital.

这个项目的目的是开发近交系小鼠， 对低剂量戊巴比妥的不同敏感性 运动活动器。这些线被命名为戊巴比妥 敏感(PBS)和戊巴比妥不敏感(PBI)，以及对照 LINE(PBC)，将由德克萨斯大学奥斯汀分校为 辨别行为相关因素和神经化学的目的 小剂量巴比妥酸盐中毒的机制。戊巴比妥是 这个项目的原型巴比妥酸盐是基于广泛的中试 已经完工了。 这项为期五年的研究将包含一个具体的目标，即 对哪些小鼠进行运动活动测试以响应 戊巴比妥，然后通过至少14次选择进行选择和繁殖 几代人。在育种和选择过程的不同阶段， 这些线路将被“特色化”(第二个具体目标)。 对较高剂量的戊巴比妥的不同反应。参数设置为 在这些线路上测量的将是休眠时间(翻正反射丧失)， 体温过低，以及对睡眠时间的耐受性。在第三个具体目标中，一个 探索戊巴比妥差异性反应的“机制” 在这些项目中，将通过对戊巴比妥的研究 清除；对乙醇、其他催眠药、苯二氮卓类药物的反应 阿片类拮抗剂和安非他明；以及大脑区域水平和 多巴胺周转，以及脑区合成和浓度 阿片肽。 我们的假设是，这些线将有助于研究 与低血压时出现的中毒有关的特定神经化学变化 给出了剂量的巴比妥酸盐。拟议的研究将提供 巴比妥酸盐醉人作用机制的研究进展 在小鼠身上，也许在人身上，在可滥用剂量的 戊巴比妥。