Department of Pharmacology and Toxicology, Center for Molecular Biosciences Innsbruck and Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
PLoS One. 2011 Feb 28;6(2):e16849. doi: 10.1371/journal.pone.0016849.
The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.
焦虑症的发病倾向被认为是由遗传和环境因素决定的。在这里，我们研究了特质焦虑的遗传倾向与病理性老鼠模型中的基于经验的习得性恐惧之间的关系。雄性 CD-1 老鼠选择性地在高架十字迷宫上繁殖，表现出高（HAB）或正常（NAB）的焦虑相关行为，然后对其进行经典的恐惧条件反射。在条件反射过程中，两条老鼠线的冻结行为都显示出了更强的恐惧反应。然而，24 小时后，与 NAB 老鼠相比，HAB 老鼠对环境或提示刺激的条件反应更明显。有趣的是，在恐惧条件反射后 6 小时甚至 1 小时，HAB 老鼠的冻结水平很高，但 NAB 老鼠没有。这些结果表明，特质焦虑决定了 HAB 线更强的恐惧记忆和/或抑制恐惧反应的能力较弱。HAB 老鼠的增强的恐惧反应可以通过用 α(2,3,5)-亚单位选择性苯二氮䓬部分激动剂 L-838,417、皮质酮或选择性神经激肽-1 受体拮抗剂 L-822,429 进行治疗来减弱。总体而言，HAB 老鼠线可能代表了一个有趣的模型：(i) 用于确定导致误导性条件恐惧反应的生物学因素，以及 (ii) 用于研究治疗与恐惧相关的疾病（包括创伤后应激障碍和恐惧症）的新型抗焦虑药理学治疗方法。
