6579 Neuroendocrine Signatures of Social-Defeated Stress Expressed by Adrenal Hormones in Mice

Abstract Disclosure: J. Noh: None. J. Choi: None. S. Myung: None. M. Kim: None. M. Choi: None. While psychological stress is one of the prevalent contributors to depression, the precise role of metabolic phenotypes in the development of depression remains elusive. Abnormality in hypothalamus-pituitary-adrenal (HPA) axis is a classical feature of depression. Here, an animal model of social defeat stress (SDS) was established with five-week-old C57BL/6J mice to repeated episodes of social defeat for a period of 10 days, facilitated by an aggressive CD-1 mouse. Liquid chromatography-mass spectrometry-based profiling of 29 adrenocortical steroids and 6 medullary amines was employed for serum samples collected at 3, 5, 7, and 10 days during the modeling from both control (n = 28) and SDS (n = 32) group. In response to initial stress, corticosterone (B) and its two precursors were significantly increased (p < 0.03 for all) during 3 days, while 18-hydroxyB was remarkably elevated (p < 0.003 for 3 days and p < 0.005) in SDS mice. In contrast, dopamine (p < 0.03) and metanephrine (p < 0.008) were significantly increased during 5 days in SDS mice, while remarkably higher levels of norepinephrine were also observed during 7 days (p < 0.01). The SDS mice showed the increased levels of normetanephrine for all days of repeated stress exposure (p < 0.002 for all, except 10 days of p < 0.02). In this study, the HPA regulated negative feedback in short period, whereas sympathetic nervous system was continuously stimulated during repeated stress exposure. The present study may provide insight into the neuroendocrine effects of social stress on allostatic overload. Presentation: 6/2/2024