Maternal separation only makes depressive tendency in C57BL/6J mice

【摘要】：Objective Early adverse experience is an important risk factor of depression,but there are disputes whether maternal separation animal model,which imitate early experienced,have depressive behavior.This article focused on maternal separation mice's behavior characteristics and the relevant mechanism.Methods The C57BL/6J mice were subjected to lOd maternal separation(MS) stress after birth,then undisturbed under dam's caring and weaning.When pups grow up to 12-20w,their behavior profiles were observed by open field test,elevated plus maze,appetitive decision-making,avoid decision-making through our self-made behavior device.After mice sacrificed,serum corticosterone was detected by radioimmunoassay,brain c-fos,serotonin(5-HT),glucocorticoid receptor(GR) and11 p-hydroxysteroid dehydrogenase 2(llp-HSD2) expression by immunohistochemistry.Results Compared with control mice,MS mice spent significantly less time in central zone in open field test(P0.01),but their behavior had no changes in elevated plus maze,the time of appetitive and avoidance decision-making all became slow obviously.Serum corticosterone was significantly elevated in DEX / CRH test(P0.01) but not after stress.In brain 5-HT expression in dorsal raphe nuclei became weaken,c-fos reaction to restrain stress blunted in several brain regions,such as prefrontal cortex,hippocampal CA1 area,and central nuclei of amygdala,but GR,which is important to feedback of hypothalamic-pituitary-adrenocortical(HPA) axis,only decreased in nucleus accumbens,and llp-HSD2,which can degrade glucocorticoids and regulate the access of glucocorticoids to the steroid receptors,decreased in many brain regions.Conclusion Maternal separation stress could make behavior more caution,HPA axis disinhibition and excitability bias,thus maternal separation have not mold any depressive-like behavior and should not be used as a depression animal model.It only facilitates depressive tendency with blunted stress reaction.