Effects Of Long-term Social Defeat On Emotion And Social Behavior Of Adult Female Brown Vole With Different Coping Strategies And The Regulatory Role Of 5-HT System

Coping is the inevitable result of facing any stressful situation,and the homeostatic response mechanism is the main means of the individual to cope with stress.People face different forms of stress in their lives.It is worth noting that most people successfully adapt to these stressors and maintain healthy behaviors and physiological functions.Only 20%-25%of individuals exposed to severe stress events can develop into depression.Obviously,it is not that the every individual suffers from a certain stress-related disease,but that there are usually susceptible individuals who exhibit specific behavior and physiological characteristics under fairly specific environmental conditions.Coping strategy is a comprehensive and complex response made by the body in the face of challenges.It affects the resistance/susceptibility to the risk of mental illness by adjusting the adaptive/non-adaptive stress response strategy.The potential mechanism underlying coping with stress can be explored through the process of social defeating stress.Active coping is usually manifested as coping with challenges and confronting fear.In rodent social encounters,it manifests as attacks,defenses,explorations,and escapes.Passive response is to avoid conflict,which is manifested in the behavior of submission,avoidance,and rigid immobility in social encounters.When an animal responds to a single acute social stress,it generally adopts the initial coping style,but whether the chronic social defeat stress change the animal's coping strategy and the chronic social defeat stress produced different effects on emotion and social behavior in animals with different coping strategies are still unclear.The serotonin system is closely related to coping strategies.The medial prefrontal cortex is closely related to cognitive decision-making and other behaviors,and receives input from the brainstem,such as the dorsal raphe nucleus.So does the serotonin system participate in the regulation and response to the chronic social defeat stress in animals with different coping strategies?Due to the stages of brain development,brain is easily affected by the external environment in puberty.At present,most studies on effects of chronic social defeat stress focus on puberty.In recent years,the birth rate of newborns in our country has continued to decline,and the problem of social population aging has gradually become prominent.In this era,the physiological and psychological pressures on adults are increasing rapidly.Research on stress in adulthood has become a problem that cannot be ignored.Among them,females are more sensitive to external stress than males.However,in most traditional rodent models,female rodents usually do not show spontaneous aggressive behavior towards same-sex individuals,which limits the study social defeat of stress in the female rodent.The mandarin vole has the characteristics of monogamy,high sociality,low anxiety,and spontaneous aggression of male and female individuals on the same sex,which provides favorable animal models for study chronic social defeat stress on emotions and social behaviors and related research on coping strategies in the females.In this experiment,the resident-intruder model was used to study the relationship between chronic social defeat stress,coping strategies,emotions,social behaviors and the serotonin system in adult female mandarin voles.The experiment mainly includes the following contents:the division of adult female mandarin vole populations with different coping strategies,behavioral testing,exploration of related molecular mechanisms,and the chemogenetic manipulations of specific projection.The behavioral experiments include:open field,elevated plus maze,tail suspending test and forced swimming test were used to test the emotions of adult female mandarin vole with different coping strategies after CSDS;social approach and avoidance experiment,three-box test experiment and social interaction were used to evaluate the sociality and social cognition.In the molecular experiment part,immunofluorescence staining experiments were used to detect the expression of TPH2 in the brain region of the dorsal raphe nucleus and the co-expression of TPH2 and c-fos protein;based on the above behavioral and molecular experimental results,chemogenetics techniques were used to activate/inhibit the DRN-mPFC 5-HT pathway to test whether this projection is involved in these behaviorsBehavioral test results:(1)The results of the open field test and the elevated plus maze test showed that there was no difference in the anxiety-like level between the active coping group and the passive coping group female mandarin voles.CSDS did not affect the anxiety of the active coping group and the passive coping group female mandarin voles.(2)The results of tail suspension test and forced swimming test showed that there was a difference in the depression-like level of female mandarin voles between the active and passive coping groups.Both the active group and passive coping females had significant depression-like behaviors after experiencing CSDS.However,the level of depression in the active group is still lower than that of the passive group;(3)The social approach avoidance test results show that there is no difference in the sociality of the active coping group and the passive coping group.CSDS reduced the sociality of the passive coping group.(4)Three-chamber social recognition test results show CSDS led to social cognitive and sociality disorder in passive coping female mandarin voles,but did not affect active coping;(5)The results of social interaction experiments show that CSDS reduced attacking,defense,social exploration,non-social exploration and long-distance exploration behaviors,but increased rigidity,immobility,avoidance.CSDS reduced social exploration behaviors of active coping female mandarin vole.(6)The pain sensitivity of the active response group and the passive response group was tested using a hot plate pain tester.It was found that the pain sensitivity of the active response group and the passive response group was different,and the pain sensitivity of the active response group was significantly higher than that of the passive response group.CSDS did not significantly affect the pain sensitivity of adult female mandarin vole with different coping strategies.The results of molecular experiments showed that CSDS reduced the number of 5-HT neurons in the DRN brain area in passive coping female mandarin vole,and had no effect on the active coping group;CSDS increased expression of cFos in the DRN of active coping and passive coping female mandarin voles..The results of chemogenetics experiments show that the specific activation of the 5-HT DRN-mPFC pathway can lead to an increase in depression-like behaviors and a decrease in sociality in active coping female mandarin vole males,but did not affect their social cognition level.However,specifically inhibiting 5-HT The DRN-mPFC pathway resulted in a decrease in depression-like behaviors and an increase in social cognition in passive coping female mandarin voles without affecting their social cognition level.Specific activation/inhibition of 5-HT DRN-mPFC pathway has no effect on the anxiety-like behavior of adult female mandarin voles with different strategies.In summary,(1)before CSDS,adult female mandarin voles with different coping strategies showed no significant difference in anxiety-like emotion and sociality,they all showed low anxiety-like level and high sociality,but the depression-like behavior and social cognition level of active coping was lower than passive coping.(2)After CSDS,CSDS did not produce different effects on anxiety-like and social behaviors in female mandarin vole with different coping strategies,but affacted depression-like behaviors differently.The depression-like level of the active group is lower than that of the passive group after CSDS.Chronic social defeat stress changed the coping strategies of adult female mandarin voles,and mad the passive coping towards a more passive trend,the impact of CSDS on the passive coping group is far greater than that of the active coping group.CSDS leads to a significant increase in depression-like levels in the passive coping group,a decline in sociality,and a high degree of social avoidance behavior.It has no effect on the active coping group,and the active coping group shows resistance to stress.The passive response group belongs to the stress-susceptible group,and the stress response of the active response group is lower than that of the passive response group.Chemogenetics experiments show that the 5-HT DRN-mPFC pathway is involved in the regulation of coping strategies.CSDS may affect the 5-HT DRN-mPFC pathway and affect the depression-like emotions and social behaviors of adult female mandarin voles with different coping strategies.5-HT DRN-mPFC pathway may be involved in the regulation of depression-like emotions and social levels,but has no obvious regulatory effect on anxiety-like emotions and social cognition levels.