Razzoli Maria, Roncari Elisa, Guidi Alessia, Carboni Lucia, Arban Roberto, Gerrard Phil, Bacchi Fabrizio
Behavioural Neuroscience Department, GlaxoSmithKline S.p.A, Psychiatry CEDD, Via Alessandro Fleming 4, 37135 Verona, Italy.
Horm Behav. 2006 Aug;50(2):245-51. doi: 10.1016/j.yhbeh.2006.03.007. Epub 2006 Apr 24.
To develop a socially based model of anxiety, the contextual fear conditioning properties of social defeat were examined in rats. Social threat consisted of exposing intruders to aggressive residents in resident home cage, separated by a partition. During 3 daily encounters, intruders were either defeated or threatened by residents, providing the defeated-threatened (DT) and threatened-threatened (TT) groups respectively. On Day 4, both DT and TT animals were subjected to a social threat only. Additional animals received a 4-day exposure to a novel empty cage (EC group). Further DT, TT, and EC rats were confronted to a different context on Day 4. DT rats exhibited a robust and context-specific anxiety-like response, characterized by significant behavioral and biochemical alterations. DT rats showed increased risk assessment and decreased exploration compared to TT and EC rats that in turn were not different towards each other. DT and TT rats exhibited increased ACTH levels, while only DT rats showed enhanced corticosterone and decreased testosterone levels compared to EC. These differences were context-specific since they were absent confronting animals to a different context and since they were not long lasting. Overall, these data demonstrate the induction of an anxiety-like state in rats through a context conditioning process based upon social factors. The social basis of this paradigm offers good face validity with anxiety disorders, which in humans are mainly related to social factors and associated with HPA axis deregulations. The present procedure may provide a useful experimental model to further investigate the neurobiological mechanisms underlying anxiety-related disorders.
为了建立一种基于社会因素的焦虑模型，研究人员在大鼠中检验了社会挫败的情境恐惧条件反射特性。社会威胁包括将入侵者置于居住笼中，与具有攻击性的居住者隔着隔板接触。在为期3天的每日接触中，入侵者要么被居住者击败，要么受到威胁，分别形成被击败-受威胁（DT）组和受威胁-受威胁（TT）组。在第4天，DT组和TT组动物仅面临社会威胁。另外的动物在一个新的空笼中暴露4天（EC组）。在第4天进一步让DT组、TT组和EC组大鼠面对不同的情境。DT组大鼠表现出强烈的、情境特异性的焦虑样反应，其特征为显著的行为和生化改变（与TT组和EC组大鼠相比，DT组大鼠表现出风险评估增加和探索减少，而TT组和EC组大鼠之间没有差异）。DT组和TT组大鼠的促肾上腺皮质激素（ACTH）水平升高，而与EC组相比，只有DT组大鼠的皮质酮水平升高，睾酮水平降低。这些差异具有情境特异性，因为当动物面对不同情境时这些差异不存在，而且这些差异并非持久存在（总体而言，这些数据表明通过基于社会因素的情境条件反射过程可在大鼠中诱导出焦虑样状态。这种范式的社会基础与焦虑症具有良好的表面效度，而人类焦虑症主要与社会因素相关并伴有下丘脑-垂体-肾上腺（HPA）轴失调。本实验方法可能为进一步研究焦虑相关障碍的神经生物学机制提供一个有用的实验模型）。 （注：括号内内容为补充完整逻辑后的意译，原文表述稍显逻辑跳跃）
