Role of Neuropeptide S in animal models of pathological fear

恐惧最有利于大脑和身体为危险情况做好准备，这有助于人类和动物应对潜在的危险事件。潜在恐惧机制的功能障碍会导致不适应的恐惧。这种不适应恐惧的一些临床表现是创伤后应激障碍或恐慌症。多项临床研究发现，神经肽S受体基因的多态与惊恐障碍发病率的增加有关。此外，已识别的NPS受体风险等位基因与不利的发育状况(这里指的是儿童期虐待)相互作用。这些发现促使神经科学家研究NPS及其受体在正常恐惧和焦虑动物模型中的作用。然而，令人惊讶的是，在病理性恐惧的动物模型中，关于NPS及其受体的研究很少。这样的模型将特别适合于探索基因环境的相互作用。因此，本研究的目的是探讨NPS及其受体在病理性恐惧动物模型中的作用。首先，将在创伤后应激障碍和惊恐障碍的动物模型中表征NPS受体缺陷的转基因小鼠的表型。然后，将研究发育条件(丰富的环境、社会压力)对野生型和NPS受体缺陷动物表型的额外影响。最后，我们想测试注射NPS是否可以阻止病理性恐惧的发展。这项拟议的研究的目的是增加我们对NPS及其受体在正常和病理性恐惧中的作用的理解。我们希望我们的数据能够为NPS受体激动剂的药物治疗的发展做出贡献。

Fear optimally prepares the brain and body for dangerous situations, which helps humans and animals cope with potentially dangerous events. Dysfunctions within the mechanisms underlying fear can lead to maladaptive fear. Some clinical manifestations of such maladaptive fear are post-traumatic stress disorder or panic disorder. Several clinical studies identified a polymorphism in the neuropeptide S (NPS) receptor gene that is associated with an increased incidence of panic disorder. Moreover, the identified risk allele of the NPS receptor interacts with unfavorable developmental conditions (here: childhood maltreatment). These findings motivated neuroscientists to investigate the role of NPS and its receptors in animal models of normal fear and anxiety. However, there is surprisingly little research on NPS and its receptor in animal models of pathological fear. Such models would be especially suitable to explore gene environment interactions. Therefore, the aim of the proposed study is to explore the role of NPS and its receptor in animal models of pathological fear. First, the phenotype of transgenic mice with a deficiency of the NPS receptor will be characterized in animal models of post-traumatic stress disorder and panic disorder. Then, the additional effects of developmental conditions (enriched environment, social stress) on the phenotype of wildtype and NPS receptor-deficient animals will be studied. Lastly, we want to test if NPS injections can block the development of pathological fear. The aim of the proposed study is to increase our understanding of the role of NPS and its receptor in normal and pathological fear. We hope that our data can contribute to the development of pharmacological therapies with NPS receptor agonists.