The Construction Of Postpartum Social Stress Animal Model And Its Impairment Mechanism On Maternal Behavior In Rats

Social stress,including witnessing violence and trauma,can induce depression,anxiety and other psychosocial disorders.It has been proved that witnessing other's continuous social frustration as a social stressor can evoke the depression like behaviors in female rats.However,there is no research focus on how the maternal behavior of postpartum female rats will change after experiencing social stress.Maternal behavior is very important to the health of the mother and the development of the offspring.Stress affects and impairs the cognitive and emotional functions that closely related to the expression of maternal behavior,and also increases the risk of mental disorders,such as depression and post-traumatic stress disorder.Both maternal care and maternal aggression are parts of maternal behavior,which respectively represent the behavior related to pups and defensive aggression against potential threats.Some of the stress animal models are mixed with physiological damage during the process of modeling,which is not conducive to the analysis and research of psychological function;the other are mainly explores the pharmacological evaluation and pathological feedback mechanism through long-term stress,which has high validity in drug prediction,but not suit for the research of cognitive neural function.To sum up,the above paradigms are not suitable for the study of postpartum maternal behavior.Therefore,this study uses strange male rats as stressor to construct a new postpartum social stress model,and aim to explore the effect of postpartum social stress on maternal behavior and its mechanism.Firstly,the validity of the model was verified by setting up the stress source of female rats.Secondly,the differences of neurotransmitter gene expression level of female rats in the postpartum social stress groups were analyzed by biochemical detection,integration to explore the physiological and chemical changes of postpartum social stress impairing maternal behavior and its potential interaction brain area.Finally,the possible brain areas were selected for intervention to find the effect of postpartum social stress on maternal behavior.The impairment mechanism of maternal behavior provides the basis for postpartum social stress drug treatment.Study 1 investigated the effects of postpartum social stress on depression like behavior,anxiety like behavior and postpartum maternal behavior,expression from the perspective of building animal model.In the experiment,strange male rats were introduced into the cage of postnatal female rats for two hours during five consecutive days,and the experiment was conducted and recorded in the presence of the pups.To investigate the extent to which the stress effect of strange male rats on postpartum mother rats can affect the maternal behavior.The results showed that the females in the social stress group showed shorter licking and lactation behaviors on the fourth and eighth day of postpartum,and longer lactation behaviors and more pups were retrieved in the test of home cage maternal behavior in the late postpartum period.The death of pups only occurred in the postpartum social stress group.Used females in the postpartum social stress group showed a longer period of rigid immobility in the forced swim test,but there was no anxiety like behavior in the open field test.In the experiment of using unfamiliar female rats to repeat the same procedures,no significant difference was found between the control group and the stress group.The results showed that the normal expression of maternal behavior was destroyed by the social stress paradigm of postpartum.It was necessary to use strange male rats as the stressor for the emergence of postpartum social stress effect.The influence of postpartum social stress on maternal behavior could work by increasing the production of depression like behavior.There was an interaction between postpartum social stress and maternal behavior,but the brain area and nerve area interacted with each other The mechanism needs to be further explored.Study 2 examined the central neural network that may interact with maternal behavior in order to explore the gene expression associated with postpartum social stress.24 hours after the end of the behavioral test in Experiment 1,the brain of the postnatal mother rats was anesthetized,and the hypothalamus,medial prefrontal lobe,striatum and hippocampus were removed and stored in a refrigerator of-80 ° C.Quantitative real-time PCR detection system(qPCR)was used for quantitative analysis of gene expression.The results showed that compared with the control group,the expression of corticotropin releasing hormone(CRH)and its type 1 receptor in the hippocampus of postnatal stress group was increased;the expression of serotonin 2C receptor(5-HT2C)in medial prefrontal lobe was decreased;the expression of dopamine 2 receptor(D2)in striatum was decreased,the expression of CRH in hypothalamus was increased.The results showed that the expression of CRH in hippocampus and hypothalamus increased in the stress group,but there was no significant change in other brain areas compared with the control group.It is suggested that the abnormal expression of dopamine D2 receptor and 5-HT2 C receptor is related to the damage of maternal behavior induced by social stress.Based on the previous studies,it is suggested that the abnormal maternal behavior may be caused by the over activation of D2 receptor in striatum,which is caused by social stress after childbirth.Study 3 used pharmacological intervention to explore whether inject the antagonist of dopamine D2 receptor injected into NAc can regulate the influence of postpartum social stress on maternal behavior.According to the results of Experiment 2 and previous findings in rodent stress model,depression like behavior and reward related defects are related to nucleus accumbens in striatum(NAc)is closely related to the functional and morphological changes.Therefore,NAc is selected as the target brain area.After one week of pregnancy,the mother rats underwent stereotactic brain localization and implanted cannula in NAc shell area.On the third day,the eighth day and the tenth day after delivery,the animals in different groups were injected with normal saline,5.0 and 20.0 mg/kg of raclopride.The results showed that: high dose antagonism of dopamine D2 receptor(20.0 mg/kg)in NAc could restore the impair of postpartum social stress on maternal behavior to a certain extent,while low dose did not.The recovery effect was not due to the inhibition of spontaneous activity,because there was no significant difference in spontaneous activity among the four groups.It is suggested that striatum is the brain area where postpartum social stress interacts with maternal behavior.The abnormal expression of dopamine D2 receptor gene is the cause of damaging the expression of maternal behavior.Antagonizing dopamine D2 receptor in NAc can regulate the damaging effect of postpartum social stress on maternal behavior,and has no significant effect on the spontaneous activity of postpartum rats.In summary,the present study reveals that the animal model of postpartum social stress has been successfully constructed by using strange male rats as the paradigm of social stress source.The impairment effect of postpartum social stress on maternal behavior is accompanied by the increase the depression like behavior,but does not affect anxiety like behavior.Postpartum social stress leads to the over activation of dopamine D2 receptor in striatum and the increase of CRH receptor expression in hippocampus and hypothalamus.Inhibition of D2 receptor expression in NAc shell area can reverse the damage of postpartum social stress on maternal behavior,indicating that striatum is the brain area where social stress and maternal behavior interact.This study further revealed the important role of NAC in maternal behavior and social stress behavior.Our study helps to improve the understanding of the neurophysiological mechanism between postpartum social stress and maternal behavior,and enhanced the understanding of D2 receptor in the pathogenesis of mental disorders such as postpartum depression.Future research will further pay more attention to the neural circuits of dopamine system in regulating maternal behavior,combining with the regulation of dopamine system on social stress behavior,which provides a new explanation for the abnormal postpartum maternal behavior caused by social stress.