Department of Behavioral and Molecular Neurobiology, Faculty of Biology and Preclinical Medicine, University of Regensburg, Regensburg, Germany.
Neuropsychopharmacology. 2012 May;37(6):1433-43. doi: 10.1038/npp.2011.329. Epub 2012 Jan 11.
Social anxiety disorder (SAD) is a major health concern with high lifetime prevalence. The current medication is rather unspecific and, despite considerable efforts, its efficacy is still unsatisfactory. However, there are no appropriate and specific animal models available to study the underlying etiology of the disorder. Therefore, we aimed to establish a model of specific social fear in mice and use this social fear conditioning (SFC) model to assess the therapeutic efficacy of the benzodiazepine diazepam and of the antidepressant paroxetine; treatments currently used for SAD patients. We show that by administering electric foot shocks (2-5, 1 s, 0.7 mA) during the investigation of a con-specific, the investigation of unfamiliar con-specifics was reduced for both the short- and long-term, indicating lasting social fear. The induced fear was specific to social stimuli and did not lead to other behavioral alterations, such as fear of novelty, general anxiety, depression, and impaired locomotion. We show that social fear was dose-dependently reversed by acute diazepam, at doses that were not anxiolytic in a non-social context, such as the elevated plus maze. Finally, we show that chronic paroxetine treatment reversed social fear. All in all, we demonstrated robust social fear after exposure to SFC in mice, which was reversed with both acute benzodiazepine and chronic antidepressant treatment. We propose the SFC model as an appropriate animal model to identify the underlying etiology of SAD and possible novel treatment approaches.
社交焦虑障碍（SAD）是一个严重的健康问题，终身患病率很高。目前的药物治疗相当不具体，尽管付出了相当大的努力，但疗效仍不尽如人意。然而，目前还没有合适的、专门针对该疾病的动物模型来研究其潜在病因。因此，我们旨在建立一种特定的社交恐惧小鼠模型，并使用这种社交恐惧条件反射（SFC）模型来评估苯二氮䓬类药物地西泮和抗抑郁药帕罗西汀的治疗效果；这些药物目前用于 SAD 患者。我们发现，通过在调查同种动物时给予电脚刺激（2-5，1 秒，0.7 mA），无论是短期还是长期，对陌生同种动物的调查都会减少，表明存在持久的社交恐惧。这种诱发的恐惧是针对社交刺激的，不会导致其他行为改变，如对新奇事物的恐惧、一般焦虑、抑郁和运动功能受损。我们发现，社交恐惧可以被急性地西泮剂量依赖性地逆转，而这种剂量在非社交环境下（如高架十字迷宫）没有抗焦虑作用。最后，我们发现慢性帕罗西汀治疗可以逆转社交恐惧。总之，我们在小鼠中展示了暴露于 SFC 后的强烈社交恐惧，这种恐惧可以通过急性苯二氮䓬类药物和慢性抗抑郁药物治疗来逆转。我们提出 SFC 模型作为一种合适的动物模型，用于确定 SAD 的潜在病因和可能的新治疗方法。
