Hierarchical status predicts behavioral vulnerability and nucleus accumbens metabolic profile following chronic social defeat stress
| Autor: | Aranzazu Duque, Carmen Sandi, Thomas Larrieu, João M. F. Rodrigues, Antoine Cherix, Rolf Gruetter, Hongxia Lei |
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| Předmět: |
0301 basic medicine
Male Early life stress Nucleus accumbens Biology General Biochemistry Genetics and Molecular Biology Nucleus Accumbens Social defeat 03 medical and health sciences Mice 0302 clinical medicine Animals Chronic stress Social Behavior CIBM-AIT Dominance hierarchy Mice Inbred C57BL 030104 developmental biology Social Dominance Metabolome Stress vulnerability General Agricultural and Biological Sciences 030217 neurology & neurosurgery Metabolic profile Stress Psychological Clinical psychology Social status |
| Popis: | Extensive data highlight the existence of major differences in individuals’ susceptibility to stress [1; 2; 3 ; 4]. While genetic factors [5 ; 6] and exposure to early life stress [7 ; 8] are key components for such neurobehavioral diversity, intriguing observations revealed individual differences in response to stress in inbred mice [9; 10; 11 ; 12]. This raised the possibility that other factors might be critical in stress vulnerability. A key challenge in the field is to identify non-invasively risk factors for vulnerability to stress. Here, we investigated whether behavioral factors, emerging from preexisting dominance hierarchies, could predict vulnerability to chronic stress [9; 13; 14; 15 ; 16]. We applied a chronic social defeat stress (CSDS) model of depression in C57BL/6J mice to investigate the predictive power of hierarchical status to pinpoint which individuals will exhibit susceptibility to CSDS. Given that the high social status of dominant mice would be the one particularly challenged by CSDS, we predicted and found that dominant individuals were the ones showing a strong susceptibility profile as indicated by strong social avoidance following CSDS, while subordinate mice were not affected. Data from 1H-NMR spectroscopy revealed that the metabolic profile in the nucleus accumbens (NAc) relates to social status and vulnerability to stress. Under basal conditions, subordinates show lower levels of energy-related metabolites compared to dominants. In subordinates, but not dominants, levels of these metabolites were increased after exposure to CSDS. To the best of our knowledge, this is the first study that identifies non-invasively the origin of behavioral risk factors predictive of stress-induced depression-like behaviors associated with metabolic changes. |
| Databáze: | OpenAIRE |
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