Depressive-like Behaviors Of Mice Induced By Social Defeat And The Effects Of Spatial Learning Tasks On Depression

Objective:To develop depressive animal model by social defeat stress, then evaluate the depression-like behavior of mice and screen susceptible ones by social avoidance test, we investigate the spatial learning and memory of susceptible mice suffering social defeat and the impact of learning and memory task on stress effect. And also the expression level of ERK, P-ERK, and PSD-95 in hippocampus.Method:1. Establishment of depressive animal model: C57BL/6 mice C57 mice were given psychological stress of social defeat for 21 days. We evaluated the depressive behaviors through social interaction experiment, open field test and sucrose preference test after 24 hours of the end of stress and screened the stress susceptible ones and stress resistance ones2. Evaluation of spatial learning memory ability of mice: We evaluated the spatial learning and memory ability of tested mice by morris water maze for 12 days, includ-ing spatial acquisition,spatial reversal, probe and reversal probe trial.3. Impact of spatial learning and memory task on stress effect: 48 hours after Morris water maze, we evaluated the impact of spatial learning and memory on stress induced depressive behavior by social interaction test, open field test and sucrose preference test.4. Impact of equal swim on stress effect: in order to balance the bias of swim in Morris water maze, the tested mice swim for the same time in the water maze without a platform during 12 days. After 48 hours, we assessed the impact of equal swim on stress induced depressive behavior through social interaction test, open field test and sucrose preference test.5. After behavior evaluation, the expression of synaptic marker PSD-95 by and the expression change of ERK,P-ERK in hippocampus were detected by immunohistochemistry and western blotting, respectively.Results:1. Screening of social defeat stress susceptible mice and behavior evaluationCompared to the control group, 40-60% mice had notable depressive-like behavior of social avoidance, which are defined as stress susceptible mice. In open field test, stress susceptible mice and unsusceptible mice have significant decrease in exploring behavior. In sucrose preference test, stress susceptible mice have significant decrease in sucrose preference compared to the control. There was no significant difference between control group and stress unsusceptible group.2. Effect of social defeat stress on spatial learning and memory of mice.In spatial acquisition, spatial reversal, probe (and reversal) trial of morris water maze, stress susceptible mice, stress unsusceptible ones and the control group reached to the platform more quickly day by day and there was no significant difference among those groups. It showed that social defeat stress did not impair spatial learning and memory.3. Impact of spatial learning and memory task on stress effectMorris water maze training significantly improved the depressive-like behavior of social avoidance for stress susceptible mice in social interaction test, open field test and sucrose preference test, while stress unsusceptible group and the mice in control group had no significant difference in above tests.4. Impact of equal swim on stress effectEqual swim training did not obviously improve the social avoidance depressive-like behavior of stress susceptible mice in social interaction test, while stress unsusceptible mice and the control group have no significant change. in open field test and sucrose preference test, we obtained similar results.5. Expression change of PSD-95 in hippocampus CA3 area after social defeat stress and the expression change improved by morris water maze training after social defeat stress.â‘ compared to the control group, stress susceptible mice had significant decrease in expression of PSD-95 in hippocampus CA3 area after social defeat stress and stress unsusceptible mice had no significant difference .â‘¡after 12-day Morris water maze training, the expression level of PSD-95 in hippocampus CA3 area in susceptible mice was identical to the control,which was higher than the susceptible group without Morris water maze training; the expression level of PSD-95 in hippocampus CA3 area in unsusceptible mice had no significant change after Morris water maze training, which was similar with the control group. 6.the expression change of ERK and P-ERK in hippocampus after social defeat stress and the expression change after social defeat stress improved by Morris water maze training.Compared to unsusceptible mice and the control, susceptible mice had no difference in expression of ERK1/2 in hippocampus after social defeat stress, and Morris water maze training also did not affect the expression of ERK1/2. Moreover, compared to unsusceptible mice and the control, susceptible mice had significant decrease in expression of P- ERK1/2, while Morris water maze spatial learning memory training could significantly enhance the phosphorylation level of ERK1/2 in hippocampus of all groups and interrupt the down-regulation of P-ERK1/2 induced by social defeat stress.Conclusion:1. 40-60% mice had depressive-like behavior such as social avoidance, decrease in exploratory behavior and sucrose preference after social defeat stress.2. Stress susceptible mice and unsusceptible ones both had no obvious impairment in spatial learning and memory, which showed that social defeat stress had no effect on spatial learning memory.3. Spatial learning and memory training could significantly improve the depressive-like behavior of stress susceptible mice, and made the expression of PSD-95 in hippocampus CA3 area back to the normal level. It showed that social defeat stress could lead to depressive-like behavior by damaging neural plasticity in stress susceptible mice, but spatial learning and memory could improve the depressive-like behavior by enhancing neural plasticity. The expression of hippocampus P-ERK had notable up-regulation after spatial learning and memory training, which demonstrated that ERK signal pathway may play a important role in this antidepressant process.4. Equal swim test results revealed that swimming in Morris water maze had no significant effect on the depressive-like behavior, which further indicated that spatial learning and memory training could improve the depressive-like behavior.