The Establishment Of Depression Model And Behavioral Research And Drug Intervention In Adolescent Female Mice

Objective:The incidence of adolescent depression has its own characteristics,and in term of this there is no significant differences between boys and girls before puberty.Once getting into puberty,the incidence of depression in adolescent female would increase dramatically,which is about 2-3 times than that in adolescent male.However,the current study of depression mainly focus on adult human beings and male rodents,and the research on adolescent depression in female is not rich enough.It has important academic significance and clinical value to discuss the effective preventions of female adolescent depression.In this paper,on the basis of reproduction the depression model with adolescent female mice,applying rapid antidepressants ketamine and GLYX-13 respectively,observe the improvement of depression-like performances and the ability of spatial memory among female adolescent mice through various behavioral tests.Methods:1.To establish depression model of adolescent female mice16 female and 16 male C57BL/6J mice postnatal 18 days(P18)were randomly divided into 4 groups: female control group,female model group,male control group and female model group,8 for each group.To establish the depression model with chronic unpredictable mild stress(CUMS).The 10 stressors included oscillation,restraint,white noise,food or water deprivation,reversal night into day,wet bedding,no bedding,cage tilt,rat bedding and so on.The model groups were received 2 different stressors every day without repeatition for 3 weeks continuously,and the degree of different stressors were increased gradually each week.During these 3 weeks,adolescent female mice were observed opening condition of their orificium vaginae everyday.After 3-week CUMS,4 groups of mice were compared their change of body weight,saccharin consumption percentage in saccharin preference test(SPT),ability of autonomous activity,travelled distance and the time spent in center in open field test(OFT),the time in open arms in elevated plus maze test(EPM),the immobility time in both tail suspension test(TST)and forced swimming test(FST).With the help of these results,we could estimate whether the adolescent female and male mice showed depression-like performances.2.The drug intervention of ketamine and GLYX-13 on depressive-like behaviors in adolescent female mice39 P18 C57BL/6J female mice were randomly divided into saline control group(Con+NS),saline model group(CUMS+NS),ketamine control group(Con+Ket),ketamine intervention group(CUMS+Ket),GLYX-13 control group(Con+ GLYX-13)and GLYX-13 intervention group(CUMS+ GLYX-13),6 groups in total,and 6 for each control group,7 for model group and each intervention group.After 3-week CUMS,comparing ability of autonomous activity of each group before and after administration of different drugs.By the results of travelled distance and the time spent in center in OFT,the time in open arms in EPM,the immobility time in both TST and FST,we could determine whether different groups of adolescent female mice showed depression-like symptoms.The results of different groups with drug intervention of ketamine or GLYX-13 were compared with those without drugs after 3-week CUMS through the comparisons of the improvement of depressive-like behaviors.3.Study on the ability of spatial memory in depressed adolescent female miceActive place avoidance(APA)can explore the spatial memory ability,cognitive coordination ability and cognitive flexibility through the performance of the mice on the turntable.The mice were divided into 6 groups as described in part 2 above.The ability of spatial learning and memory was judged by the track of movement,time of the first time to enter the shock area and the number of times to enter the shock area in APA.The improvement of ability of spatial memory was compared between the results of different groups after intervention of ketamine or GLYX-13 and those without drugs after 3-week CUMS.Results:1.After 3-week CUMS,compared with the female control group,the ability of autonomous activity decreased in female model group,and the change of body weight,saccharin consumption percentage,travelled distance,the time spent in center,the time in open arms,the immobility time in TST and FST showed significant meaning with varying degree in female model group(P<0.05 or P<0.01 or P<0.001).What`s more,compared with the male control group,the change of body weight,saccharin consumption percentage,travelled distance,the time spent in center and the immobility time in FST showed significant meaning in male model group(P<0.05 or P<0.01 or P<0.001).At the same time,the ability of autonomous activity in female model group decreased more obviously compared with the male model group.And the travelled distance,time in open arms and the immobility time in TST and FST showed significant meaning in female model group compared with male model group(P<0.05 or P<0.01).2.After reproducing 3-week CUMS,the ability of autonomous activity of each model group decreased compared with their corresponding control group.The results of behavioral tests including SPT,OFT,EPM,TST and FST in each model group were statistically significant compared with corresponding control group(P<0.05).After administration of drugs,ketamine model group and GLYX-13 model group were more active than before treatment,and ketamine model group and ketamine control group had no significant difference in terms of the ability of autonomic activity.The comparison of ketamine model group and GLYX-13 model group and the control groups showed no statistical significance(P>0.05).The travelled distance and the immobility time in TST in ketamine model group were statistically significant compared with the saline model group(P<0.05).The immobility time in FST in GLYX-13 model group showed statistical significance compared with the saline model group(P<0.05).3.After reproducing 3-week CUMS,in APA,the trajectories of Trial 1 showed that the spatial learning and memory ability of model groups were lower than that of their corresponding control groups.The first time to enter the shock area in APA of three model groups were shortened compared with the saline control group in Trial 3,which showed statistical significance(P<0.05).The number of times to enter the shock area in APA of saline model group and GLYX-13 model group showed different degrees of statistical significance compared with the saline control group in Trial 6(P<0.05 or P<0.01).After administration of drugs,the trajectory of Trial 1 showed that the spatial learning and memory ability of ketamine group and GLYX-13 model group were not significantly improved.The first time to enter the shock area was extended in ketamine model group compared with the saline model group and GLYX-13 model group in Trial 1,which was statistically significant(P<0.05 or P<0.01).The number of times to enter the shock area was decreased in ketamine model group and GLYX-13 model group compared with saline model group in Trial 1 and Trial 6,which were statistically significant,as well(P<0.05).Conclution:1.The adolescent female and male mice in the model groups were successfully reprodeced.But the depressive-like performances of female model group were more obvious than those of male model group,which indicated that the effects of same stressors on adolescent female mice more serious than those on adolescent male mice.Compared with the male model mice,the female model mice were more susceptible to CUMS,and the degree of depression were more severe.2.Both ketamine and GLYX-13 had rapid antidepressant effect,improving the depression-like performance of depressed adolescent female mice,and the level of improvement in different behavioral tests were different.3.Either ketamine or GLYX-13 could improve the ability of spatial memory of adolescent female mice with depression-like behaviors,but the improvement of ketamine was faster than that of GLYX-13.