Garrett K M, Niekrasz I, Haque D, Parker K M, Seale T W
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Behav Genet. 1998 Mar;28(2):125-36. doi: 10.1023/a:1021424108213.
The role of genotype in susceptibility to the behavioral actions of benzodiazepines is not well characterized. To develop a model for such studies, we have characterized the anxiolytic and sedative activities of diazepam in C57BL/6J and A/J inbred mice. C57BL/6J mice were more responsive than A/J mice to diazepam-induced anxiolytic-like activity in the mirrored chamber aversion assay and the elevated plus-maze assay. Basal activity of the two strains did not differ in either assay. In contrast, the two strains were equally responsive to the anxiolytic effects of the 5-HT1A receptor partial agonist, buspirone. C57BL/6J mice were also more susceptible to the sedative effects of diazepam than were A/J mice. Flumazenil blocked the effects of diazepam in these behavioral assays. Measurement of diazepam and nordiazepam in blood and brain suggested that the response differences are of a pharmacodynamic rather than a pharmacokinetic nature. Taken together, these findings indicate that C57BL/6J and A/J mice provide a valuable tool for behavioral genetic studies of the mechanisms underlying the pharmacological actions of benzodiazepines.
基因型在苯二氮䓬类药物行为作用易感性中的作用尚未得到充分表征。为了开发用于此类研究的模型，我们已对C57BL/6J和A/J近交系小鼠中地西泮的抗焦虑和镇静活性进行了表征。在镜像箱厌恶试验和高架十字迷宫试验中，C57BL/6J小鼠对地西泮诱导的抗焦虑样活性比A/J小鼠更敏感。在这两种试验中，两个品系的基础活性没有差异。相比之下，两个品系对5-HT1A受体部分激动剂丁螺环酮的抗焦虑作用反应相同。C57BL/6J小鼠对地西泮的镇静作用也比A/J小鼠更敏感。氟马西尼在这些行为试验中阻断了地西泮的作用。血液和大脑中地西泮和去甲地西泮的测量表明，反应差异是药效学性质而非药代动力学性质。综上所述，这些发现表明，C57BL/6J和A/J小鼠为苯二氮䓬类药物药理作用机制的行为遗传学研究提供了有价值的工具。
