| Objective:To explore the effects of fluoxetine(FLX) on the dendritic spines of the CA1 area, CA3 area and DG in the hippocampus formation in the of chronic unpredictable stress(CUS) rat model of depression.Methods: All the male Sprague Dawley(SD) rats(4~5weeks old, 120~160g) were fed adaptively for 2 week, and the rats whose sucrose preferences were not stable were eliminated. The rats were then divided into CUS interfered group and CUS control group. The CUS interfered group was exposed to isolation and CUS for 4 week(at least 2 kinds of unpredictable stress stimulations each day), while the control group was fed normally without any stress(5 rats per cage). The body weight and sucrose preference test(SPT) were assessed at the same time of every week. After 4-week of CUS exposure, the stress-unsusceptible rats in CUS interfered group were eliminated according to the results of SPT, and the rest CUS interfered rats were divided into CUS group and CUS+FLX group randomly. CUS+FLX group rats were given daily intraperitoneal injection with fluoxetine at the dose of 5 mg/kg while Control group rats and CUS group rats given daily intraperitoneal injection with saline. The drug injection continued for 21 days from the 5th week to the7 th week with continuous exposure to CUS. The body weight and SPT were assessed at the same time of every week. At the end of the 7th week, the open field test, the elevated plus maze and the forced swim test were performed to test the behavioral changes. The total volume of CA1 area, CA3 area and DG in the hippocampus formation, the numerical density and the total number of the dendritic spines of CA1 area, CA3 area and DG in the hippocampus formation were investigated with the stereological methods and immunohistochemical methods.Results: 1. We found that the body weight of CUS interfered group were significantly lower when compared to the control group from the 2th week to the 4h week in the first 4 weeks exposure to CUS(p < 0.01). The body weight of CUS group and CUS+FLX group were significantly lower when compared to the control group from the 5thweek to the 7h week of exposure to FLX treatment(p < 0.01). 2. The CUS interfered group showed significantly decreased sucrose preference(p < 0.05) when compared to the control group from the 2th week to the 4h week in the first 4 weeks exposure to CUS(p < 0.05). The CUS+FLX group showed significantly increased sucrose preference when compared to the CUS group from the 5th week to the 7h week of exposure to FLX treatment(p < 0.05). In the open feild test, the total movement distance, the mean speed, the time percentages and the distance percentages of the inner area in both CUS group and CUS+FLX group exhibited significant decrease when compared to control group(p < 0.05). In the elevated plus maze test, the time spent in open arms and the time percentage in the open arms were significantly decreased and the time percentage in close arms was significantly increased in CUS group and CUS+FLX group when compared to control group, respectively(p < 0.05). 3. The total volumes of CA1 area, CA3 area and DG were not significantly different among the three group rats(p > 0.05). The numerical density and the total number of the dendritic spines of CA1 area, CA3 area and DG in hippocampus of CUS group were significantly reduced when compared to the control group(p < 0.01). The numerical density and the total number of the dendritic spines of CA1 area, CA3 area and DG in hippocampus of CUS+FLX group were significantly higher than those of CUS group(p < 0.01).Conclusions: The present study demonstrated that the numerical density and the total number of the dendritic spines of CA1 area, CA3 area and DG in hippocampus formation in the rat exposure to the chronic stress were significantly decreased. After the fluoxetine treatment, the state of anhedonia was improved accompanied by the increase of the numerical density and the total number of the dendritic spines of CA1 area, CA3 area and DG in hippocampus formation. The increase in the dendritic spine numbers of the CA1 area, CA3 area and DG in the hippocampus formation of depression might be a possible mechanism in the antidepressant effect of fluoxetine. |
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