Role of Neuropeptide S in animal models of pathological fear

• Applicant: Professor Dr. Markus Fendt
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Biological Psychiatry
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 288419798

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.

• DFG Programme: Research Grants