Adolescent Escitalopram Prevents The Effects Of Maternal Separation On Depression- And Anxiety-like Behaviours And Regulates The Levels Of Inflammatory Cytokines In Adult Mice

Objective: Whether early intervention is beneficial for delaying or preventing the onset of mental illness and clarifying its related mechanisms is an urgent problem to be solved in clinical practice.However,there are few studies in this field,and the results are not consistent.Adolescence is an important period of brain development in animals.Previous studies indicated that dramatic neurobiological and physical changes occur during this period.Therefore,we focus on the inflammatory pathogenesis of depression,and we explored whether depression in adult mice induced by maternal separation(MS)can be prevented by early antidepressant intervention.Methods: Twenty-eight offspring of C57BL/6 mice were included in this study.Mice were randomly divided into four groups(n=7 for each group)according to the stress and drug intervention:(1)control + vehicle(CON-V);(2)control + escitalopram(CON-ES);(3)MS + vehicle(MS-V);and(4)MS + escitalopram(MS-ES).The methods of establishing the model for maternal separation were: postnatal day(PND)2 ~ PND9,MS for 4h(21:30 ~ 17:30);PND10~PND16,MS for 6h(15:30~21:30);PND17~PND20,MS for 8h(13:30~21:30).ES was dissolved in distilled water and injected intraperitoneally(IP)at a dose of 10 mg/kg.During adulthood,open field test was used to evaluate locomotor activity of mice.Depressive like behavior was evaluated by saccharin preference test and anxiety like behavior was evaluated by elevated plus maze.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of proinflammatory cytokines.We detected the levels of interleukins(IL)-1? and tumor necrosis factor(TNF)-? and IL-10 in the ventral hippocampus(HPV),prefrontal lobe(PFC)and serum of mice.Results: 1.There was no statistical difference between four groups in the total distance and the crossing number in open-field test(P > 0.05).2.Tthere was no significant difference in the total water consumption between the four groups(P>0.05).The saccharin preference in the MS-V group was lower than the CON-V group(P =0.004)and the MS-ES group(P <0.001).3.There was no statistical difference between four groups in the crossing number in elevated plus maze test(P>0.05).The percentage of time spent in the open arms in the MS-V group was significantly lower than the CON-V group(P =0.032).The percentage of entries into the open arms in the MS-V group were significantly lower than the CON-V group(P =0.003)and the MS-ES group(P =0.001).4.The levels of IL-1? in HPV of mice in the MS-V group were significantly higher than the CON-V group(P =0.002)and MS-ES group(P =0.003).The levels of IL-10 in HPV of mice in the MS-V group were lower than the CON-V group(P =0.008)and the MS-ES group(P =0.041).The levels of IL-1?in PFC of mice in the MS-V group was higher than the CON-V group(P =0.045).The levels of IL-1? in serum of mice in the MS-V group was higher than the CON-V group(P =0.045).Conclusion: Adolescent escitalopram could prevents the effects of maternal separation on depression-and anxiety-like behaviours and regulates the levels of inflammatory cytokines in adult mice.