Gallaher E J, Gionet S E, Feller D J
Research Service, VA Medical Center, Portland, OR 97201.
J Addict Dis. 1991;10(1-2):45-60. doi: 10.1300/J069v10n01_04.
Benzodiazepine (BZ) effects include anxiolyis, sedation, seizure protection, and muscle relaxation; the mechanisms underlying these various effects are not understood. We have recently used the rotarod test in conjunction with selective breeding techniques to develop lines of mice which are diazepam-sensitive (DS) and diazepam-resistant (DR). We review the general methods of selective breeding, along with a description of the DS/DR selection study, and then describe a variety of behavioral and neurochemical studies which have been conducted in an attempt to characterize these mice. We have investigated the effects of other sedative drugs believed to interact with the BZ receptor, including ethanol, pentobarbital, and phenobarbital. We have also tested these mice for seizure threshold and open-field activity. DS and DR mice do not differ in diazepam-induced seizure protection, suggesting that different mechanisms underlie rotarod performance and the anti-convulsant effect. These results provide evidence to support the search for nonsedating anti-convulsants. To determine the neurochemical basis for observed differences, BZ receptor density and chloride flux have been measured. We discuss the interaction between behavioral and neurochemical approaches, and describe a conceptual framework to guide future studies with these unique new animals.
苯二氮䓬（BZ）的作用包括抗焦虑、镇静、抗惊厥和肌肉松弛；这些不同作用背后的机制尚不清楚。我们最近将转棒试验与选择性育种技术结合起来，培育出了对地西泮敏感（DS）和对地西泮耐受（DR）的小鼠品系。我们回顾了选择性育种的一般方法，以及DS/DR选择研究的描述，然后描述了为试图表征这些小鼠而进行的各种行为和神经化学研究。我们研究了其他据信与BZ受体相互作用的镇静药物的作用，包括乙醇、戊巴比妥和苯巴比妥。我们还测试了这些小鼠的惊厥阈值和旷场活动。DS和DR小鼠在地西泮诱导的抗惊厥作用方面没有差异，这表明转棒试验表现和抗惊厥作用的机制不同。这些结果为寻找非镇静性抗惊厥药物提供了证据支持。为了确定观察到的差异的神经化学基础，我们测量了BZ受体密度和氯通量。我们讨论了行为和神经化学方法之间的相互作用，并描述了一个概念框架，以指导对这些独特的新动物的未来研究。
