Pacific Biosciences Research Center, University of Hawaii,1993 East-West Road, Honolulu, HI 96822, USA.
Behav Brain Res. 2011 Jan 1;216(1):446-51. doi: 10.1016/j.bbr.2010.08.039. Epub 2010 Sep 9.
BTBR T+ tf/J (BTBR) is an inbred mouse strain that shows behavioral traits with analogies to the three diagnostic symptoms of autism spectrum disorder (ASD); deficits in social interaction, impaired communication, and repetitive behaviors with restricted interests. Previous findings reveal that when compared to C57BL/6J (B6) and other inbred strains, BTBR exhibit normal to low anxiety-like traits in paradigms designed to assess anxiety-related behaviors. The current study assessed the generality of these anxiety findings. In experiment 1, B6 and BTBR mice were tested in the elevated plus maze (EPM), mouse defense test battery (MDTB) and elevated zero-maze. BTBR mice exhibited an anxiogenic profile in the EPM, with a reduction in open arm time and an increase in risk assessment behaviors, as compared to B6. In the MDTB, BTBR showed enhanced vocalization to the predator, and significantly less locomotor activity than B6 in the pre-threat situation, but significantly more locomotion than B6 following exposure to a predator threat, suggesting enhanced defensiveness to the predator. In the zero-maze, BTBR mice showed a significantly higher number of entries and time spent in the open segments of the apparatus, when compared to B6. In experiment 2, a three-chambered social preference test was used to evaluate effects of the systemic administration of an anxiolytic compound, diazepam, on B6 and BTBR social approach. Diazepam consistently increased time in the compartment containing the social stimulus, for both B6 and BTBR mice. However, in the vehicle treated groups, B6 mice spent significantly more time while BTBR mice spent significantly less time in the social stimulus compartment; after diazepam administration both B6 and BTBR strains significantly preferred the social stimulus chamber. These results suggest that while the anxiety responses of BTBR mice to novel situations (EPM and zero-maze) are inconsistent, BTBR mice appear to be more defensive to animate threat stimuli (predator or another mouse). Reduction of anxiety by diazepam normalized the social preference of BTBR for a mouse stimulus in the three-chambered test.
BTBR T+ tf/J（BTBR）是一种近交系小鼠，其行为特征与自闭症谱系障碍（ASD）的三个诊断症状具有相似性；社交互动障碍、沟通障碍以及兴趣受限的重复行为。先前的研究结果表明，与 C57BL/6J（B6）和其他近交系相比，BTBR 在设计用于评估焦虑相关行为的范式中表现出正常至低焦虑样特征。本研究评估了这些焦虑发现的普遍性。在实验 1 中，B6 和 BTBR 小鼠在高架十字迷宫（EPM）、小鼠防御测试电池（MDTB）和高架零迷宫中进行测试。与 B6 相比，BTBR 在 EPM 中表现出焦虑样特征，表现为开放臂时间减少和风险评估行为增加。在 MDTB 中，BTBR 对捕食者的发声增加，在威胁前状态下的运动活性明显低于 B6，但在暴露于捕食者威胁后，运动活性明显高于 B6，表明对捕食者的防御性增强。在零迷宫中，与 B6 相比，BTBR 小鼠进入和停留在仪器开放段的次数和时间明显增加。在实验 2 中，使用三室社交偏好测试来评估系统给予抗焦虑化合物地西泮对 B6 和 BTBR 社交接近的影响。地西泮一致增加了含有社交刺激的隔室中的时间，无论是 B6 还是 BTBR 小鼠。然而，在载体处理组中，B6 小鼠在社交刺激隔室中花费的时间明显更多，而 BTBR 小鼠花费的时间明显更少；地西泮给药后，B6 和 BTBR 品系均明显更喜欢社交刺激室。这些结果表明，尽管 BTBR 小鼠对新情况（EPM 和零迷宫）的焦虑反应不一致，但 BTBR 小鼠对动物威胁刺激（捕食者或另一只老鼠）似乎更具防御性。地西泮降低焦虑症使 BTBR 在三厢测试中对老鼠刺激的社交偏好正常化。
