SOCIAL DOMINANCE INFLUENCES ANXIETY VULNERABILITY AND MEDIAL PREOPTIC AREA TRANSCRIPTIONAL PROFILE FOLLOWING RESTRAINT STRESS

Abstract Background Social dominance is an evolutionarily conservative social internal state, and emerging evidence has demonstrated that social dominance can influence individuals’ psychological status. In the scope of stress neurobiology, investigators examined the effects of social dominance on behavioral profiles after several stressors previously. However, existing literature offered contradictory findings about the relationship between social rank and resilience towards social defeat that induced depression, and what is not yet clear is the impact of social dominance on the vulnerability of anxiogenic asocial stress. Furthermore, instead of a deeper understanding of the mechanism underpinning social hierarchy, far too little attention has been paid to the neurobiological basis of the relationship between internal social status and stress susceptibility. Aims & Objectives The objective of this research is to determine whether the social dominance of adult male rats could confer their vulnerability to anxiety after stress. This study also seeks the critical brain region and molecular components that regulate the susceptibility of anxiogenic stress among rats with different social dominant statuses. Method Here, we utilized the tube test to assess the inner-cage social dominance of adult male rats. After establishing a stable social hierarchy, the open field test and elevated plus maze were employed to evaluate the anxiety-like behavior before and after acute restraint stress, which is a proven anxiogenic stressor. To find the critical brain region that regulates stress susceptibility among rats with different social dominance, we used whole-brain c-fos mapping in the brain tissue obtained from rats with restraint stress. Then, we performed a bioinformatic analysis of differentially expressed genes (DEGs) gained from RNA sequencing (RNA-seq) data to figure out the transcriptional profiles of the critical brain region and the potential hub gene that may be responsible for the vulnerability to stress. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was conducted to confirm the hub gene finding from the RNA-seq. Results There was a significant correlation between the anxiety-like behavior after acute restraint stress and the social dominant status of adult male rats, in detail that the male rats with the highest social rank (Dom) demonstrated a higher degree of anxiety-like behavior after stress than those with the lowest social rank (Sub) in the social hierarchy. Interestingly, none of these correlations or differences were observed before stress. Further tests revealed that the activated degree of the medial preoptic area (mPOA) after stress was stronger in Dom rats than in Sub ones. 546 DEGs were obtained from RNA-seq. These DEGs were enriched in several pathways, including long-term potentiation. After restraint stress, the potential hub gene Grin2b in mPOA was expressed higher in Dom rats than in Sub ones. Discussion & Conclusion Our findings demonstrate that the male rats with higher social dominance are more vulnerable to anxiety after anxiogenic stress, and the mPOA and Grin2b are the critical brain region and the hub gene that may be responsible for the different susceptibility of anxiety after stress among male rats with distinct social dominance respectively. References 1.MASCARO, O., GOUPIL, N., PANTECOUTEAU, H., DEPIERREUX, A., VAN DER HENST, J. B. &CLAIDIè RE, N. 2023. Human and animal dominance hierarchies show a pyramidal structure guiding adult and infant social inferences. 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