PENTOBARBITAL ACTIVATION IN SELECTED MOUSE LINES

这个项目的目的是开发小鼠的远交系， 对低剂量戊巴比妥的敏感性差异 自发活动装置 这些被命名为戊巴比妥的管道 敏感（PBS）和戊巴比妥不敏感（PBI），沿着对照 线（PBC），将在德克萨斯大学奥斯汀分校开发， 辨别行为相关物和神经化学物质的目的 低剂量巴比妥中毒的机制。 戊巴比妥是 该项目的巴比妥酸盐原型基于广泛的试点测试 已经完成了。 这项为期五年的研究将包括一个“育种”的具体目标， 测试小鼠的自发活动， 戊巴比妥，然后通过至少14次选择进行选择和远系繁殖 代 在育种和选择过程的各个阶段， 这些线路将被“表征”（第二个具体目标）， 对高剂量戊巴比妥的不同反应 参数以 在这些行中测量的将是睡眠时间（翻正反射的丧失）， 体温过低和睡眠耐受性。 在第三个具体目标中， 对戊巴比妥不同反应的“机制”的探索 将通过研究戊巴比妥， 清除率;对乙醇、其他催眠药、苯二氮卓类药物、 阿片拮抗剂和安非他明;以及脑区域水平和 多巴胺的周转，大脑区域的合成和浓度， 阿片肽 假设这些线将有助于研究 与中毒有关的特定神经化学变化， 给予一定剂量的巴比妥酸盐。 拟议的研究将提供 关于巴比妥酸盐致醉作用机制的信息 在低剂量的小鼠中，以及在可滥用剂量的 戊巴比妥

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.