Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, WI 53719-1176, USA.
Genes Brain Behav. 2010 Nov;9(8):974-84. doi: 10.1111/j.1601-183X.2010.00636.x.
Behavioral inhibition (BI) is an adaptive defensive response to threat; however, children who display extreme BI as a stable trait are at risk for development of anxiety disorders and depression. The present study validates a rodent model of BI based on an ethologically relevant predator exposure paradigm. We show that individual differences in rat BI are stable and trait-like from adolescence into adulthood. Using in situ hybridization to quantify expression of the immediate early genes homer1a and fos as measures of neuronal activation, we show that individual differences in BI are correlated with the activation of various stress-responsive brain regions that include the paraventricular nucleus of the hypothalamus and CA3 region of the hippocampus. Further supporting the concept that threat-induced BI in rodents reflects levels of anxiety, we also show that BI is decreased by administration of the anxiolytic, diazepam. Finally, we developed criteria for identifying extreme BI animals that are stable in their expression of high levels of BI and also show that high BI (HBI) individuals exhibit maladaptive appetitive responses following stress exposure. These findings support the use of predator threat as a stimulus and HBI rats as a model to study mechanisms underlying extreme and stable BI in humans.
行为抑制（BI）是一种对威胁的适应性防御反应；然而，表现出极端 BI 作为稳定特征的儿童有发展焦虑症和抑郁症的风险。本研究基于一种与行为相关的捕食者暴露范式，验证了一种啮齿动物 BI 模型。我们表明，大鼠 BI 中的个体差异从青春期到成年期都是稳定的和特质性的。使用原位杂交技术来量化即时早期基因 homer1a 和 fos 的表达作为神经元激活的测量，我们表明 BI 中的个体差异与各种应激反应性脑区的激活有关，包括下丘脑室旁核和海马 CA3 区。进一步支持了啮齿动物中威胁诱导的 BI 反映焦虑水平的概念，我们还表明，苯二氮䓬类药物安定的给药可以降低 BI。最后，我们制定了识别表现出高水平 BI 的极端 BI 动物的标准，并且还表明高 BI（HBI）个体在应激暴露后表现出适应不良的食欲反应。这些发现支持将捕食者威胁用作刺激物，并将 HBI 大鼠作为研究人类中极端和稳定 BI 机制的模型。
