Fear memory generalization and social anxiety are adaptive survival mechanisms that are highly conserved across species. Fear memory generalization promotes flexible fear responses to novel situations, whereas social anxiety supports cautious behavior towards unfamiliar conspecifics in complex and constantly changing environments. However, prolonged or excessive fear/caution is maladaptive and may result in one of the anxiety disorders and trauma- and stressor-related disorders (AD-TSRD). These

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... disorders are a tremendous social and economic burden in urgent need for further research to identify novel therapeutic targets. Many clinical and animal studies have linked the neuropeptide systems of the brain, such as neuropeptide S (NPS) and orexin, with an increased risk of developing AD-TSRD and related endophenotypes. Several studies have also implicated dysfunctions of the hypothalamic-pituitary-adrenal axis to the genesis and prognosis of AD-TSRD. Therefore, understanding these cross regulations in the development of AD-TSRD-related behavioral endophenotypes, such as fear overgeneralization and dysregulation in social behavior, might be a promising strategy for novel treatments. Hence, in this thesis, I focused on understanding the complex interplay of AD-TSRD-related behavioral endophenotypes in mice with genetically altered NPS and orexin systems. Moreover, I studied how stress hormones may play a critical role in the development and progression of these endophenotypes. To this end, I designed two paradigms to induce fear memory generalization and social fear using modified fear conditioning. Both sexes of NPS receptor (NPSR)-deficient mice were tested in the paradigms for 1) the specificity and strength of the fear memory, 2) acquisition, expression, and extinction of the conditioned social fear, while orexin-deficient mice were tested only in the latter. Moreover, mice were subjected to a battery of additional behavioral paradigms (sociability test, acoustic startle response, and light-dark box) to have a comp [...]